Note: This page contains sample records for the topic meningitis cerebrospinal fluid from
While these samples are representative of the content of,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of
to obtain the most current and comprehensive results.
Last update: November 12, 2013.

Cerebrospinal fluid lactic acidosis in bacterial meningitis.  

PubMed Central

A rapid, microenzymatic method was used to measure cerebrospinal fluid lactate levels in 205 children with suspected bacterial meningitis. Fifty children with normal CSF containing fewer than 0.005 X 10(9)/l WBC, no segmented neutrophils, glucose 3.4 +/- 0.8 mmol/l (61.2 +/- 14.4 mg/100 ml), and a protein of less than 0.30 g/l had CSF lactate levels below 2.0 mmol/l (18 mg/100 ml) (mean and standard deviation 1.3 +/- 0.3 mmol/l (11.8 +/- 2.7 mg/100 ml)). In 31 cases of proved viral meningitis as with 58 cases of clinically diagnosed viral meningitis, levels were below 3.8 mmol/l (34.5 mg/100 ml), being 2.3 +/- 0.6 mmol/l (20.9 +/- 5.4 mg/100 ml), and 2.1 +/- 0.7 mmol/l (19.1 +/- 6.4 mg/100 ml) respectively. Sixty-six cases of bacterial meningitis had CSF lactate levels ranging from 3.9 mmol/l (35.4 mg/100 ml) to greater than 10.0 mmol/l (90.0 mg/100 ml). Longitudinal studies in 7 children with bacterial meningitis showed that cerebrospinal fluid lactate levels differentiated bacterial from viral meningitis up to 4 days after starting treatment with antibiotics. Use of CSF lactate measurement for monitoring the efficacy of treatment is illustrated in a case of bacterial meningitis due to Pseudomonas aeruginosa. The origin of the cerebrospinal fluid lactate acidosis and the role of lactate in the pathophysiological cycle leading to intensification of brain tissue hypoxia and cellular damage is discussed with respect to the short-term prognosis and the long-term neurological sequelae.

Eross, J; Silink, M; Dorman, D



Cerebrospinal fluid lactic acid in diagnosis of meningitis.  

PubMed Central

Quantitative lactate determinations were performed on cerebrospinal fluids to assess their value in the rapid diagnosis of bacterial and mycotic meningitis and to evaluate their value in assessing the prognosis in these patients. Cerebrospinal fluid lactate concentrations were elevated in all patients with untreated bacterial or fungal meningitis. Lactate concentrations proved very valuable in following patients with mycotic meningitis and in differentiating aseptic from bacterial meningitis. Elevated cerebrospinal fluid lactate is not specific for meningitis. Lactate is also elevated in situations where there is central nervous system ischemia and necrosis and in patients with brain tumors. Lactate concentration is normal in chronic degenerative brain diseases. Thus, the clinical situation must be taken into account when interpreting the lactate concentrations.

Komorowski, R A; Farmer, S G; Hanson, G A; Hause, L L



Neonatal meningitis: mortality, cerebrospinal fluid, and microbiological findings.  


This study describes the bacteriology, cerebrospinal fluid (CSF) findings, and mortality of neonatal meningitis over an 11-year period. The minimum incidence of neonatal meningitis at Tygerberg Hospital is 0.72/1000 live births/year. Eighty-eight patients were included in the study. Median birthweight and age at diagnosis were 2320 g and 12 days, respectively. CSF culture was positive in 77 (88 per cent), blood culture was positive in 51 (57 per cent), and Gram stain was positive in 58 (66 per cent). The most frequently cultured organisms were Group B Streptococcus, Klebsiella pneumoniae, and E. coli. Thirty (34 per cent) patients died, the majority within 72 h after admission. The death rate was significantly increased in babies with a birthweight of less than 1500 g (59 per cent). Increased total CSF protein was associated with an increased risk of death. Normal CSF cell count, total CSF protein and CSF glucose were found in six infants. PMID:10996987

Nel, E



Microscopic Examination and Broth Culture of Cerebrospinal Fluid in Diagnosis of Meningitis  

Microsoft Academic Search

We reviewed the results of microscopic Gram stain examination and routine culture for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital microbiology laboratory during 55 months. There were 56 instances of bacterial or fungal meningitis (16 associated with central nervous system (CNS) shunt infection), four infections adjacent to the subarachnoid space, four cases of sepsis without meningitis, and




Bactericidal Activity against Cephalosporin-ResistantStreptococcus pneumoniaein Cerebrospinal Fluid of Children with Acute Bacterial Meningitis  

Microsoft Academic Search

There are reports of failure of extended-spectrum cephalosporin treatment in pneumococcal meningitis. On the basis of in vitro and animal experimental studies, the addition of vancomycin or rifampin to an extended- spectrum cephalosporin has been recommended for empiric treatment of these patients. Cerebrospinal fluid (CSF) was taken from 31 children with bacterial meningitis randomized to receive ceftriaxone alone (n 511),



Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis  

Microsoft Academic Search

Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of

Ilan Dalal; Sharon Tzhori; Eli Somekh; Avigdor Mandelberg; Arie Levine; Ami Ballin



Concentrations of Cefpirome in Cerebrospinal Fluid of Children with Bacterial Meningitis after a Single Intravenous Dose  

PubMed Central

A single intravenous dose of cefpirome, 50 mg/kg, was administered to 15 children with bacterial meningitis 24 to 48 h after initiation of standard antibiotic and steroid therapy. Cefpirome concentrations in serum and cerebrospinal fluid were determined at selected time intervals. The mean (standard deviation) peak concentration in cerebrospinal fluid (n = 5) was 10.8 (7.8) ?g/ml. Drug concentrations in cerebrospinal fluid above the MIC for Streptococcus pneumoniae at which 90% of the isolates were inhibited were found 2, 4, and 8 h after the dose of cefpirome was given. The penetration of cefpirome into cerebrospinal fluid compares favorably with that of other extended-spectrum cephalosporins and suggests that this agent would be useful in the therapy of childhood meningitis, including cases caused by drug-resistant S. pneumoniae.

Friedland, Ian R.; Sultan, Eric; Lehr, Karl H.; Lenfant, Bernard



Cytokine profile in cerebrospinal fluid of children with echovirus type 4 meningitis.  


Cytokines play a role in meningeal inflammation and leukocyte recruitment. Research has demonstrated that levels of different cytokines are elevated in aseptic and viral meningitis. Unfortunately, previous data were confounded by the inclusion of multiple viral agents as a study group. The aims of the study were to determine the cerebrospinal fluid concentrations of various cytokines in an outbreak of a single viral agent and to correlate between cytokine levels and leukocytes. Cerebrospinal fluid samples, collected during an outbreak of echovirus type 4 meningitis in infants and children in Israel, were tested for routine characteristics. In addition, cytokine levels were measured in 71 meningitis patients and compared with those of 11 nonmeningitis patients. Concentrations of interleukin-6 (2417 +/- 2713 vs 28 +/- 20 pg/mL; P < 0.01) and interferon gamma (36 +/- 38 vs 4.8 +/- 0.9 pg/mL; P < 0.01) were significantly higher in patients with meningitis than in the control group, whereas soluble intercellular adhesion molecule-1 (1.12 +/- 2.6 vs 0.06 +/- 0.1 ng/mL) levels did not differ significantly. In addition, only interleukin-6 levels correlated with leukocyte counts in viral meningitis patients. Interleukin-6 was the most sensitive and specific characteristic in predicting meningitis in this homogeneous group of patients. Furthermore, only interleukin-6 correlated with leukocyte counts in the cerebrospinal fluid. PMID:14643393

Dalal, Ilan; Tzhori, Sharon; Somekh, Eli; Mandelberg, Avigdor; Levine, Arie; Ballin, Ami



Oxidative stress in cerebrospinal fluid of patients with aseptic and bacterial meningitis.  


This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS) and antioxidant defense systems such as superoxide dismutase (SOD), glutathione S-transferase (GST), reduced glutathione (GSH) and ascorbic acid. TBARS levels, SOD and GST activity increase in aseptic meningitis and in bacterial meningitis. The ascorbic acid concentration increased significantly in patients with both meningitis types. The reduced glutathione levels were reduced in CSF of patients with aseptic and bacterial meningitis. In present study we may conclude that oxidative stress contributes at least in part to the severe neurological dysfunction found in meningitis. PMID:19205881

de Menezes, Charlene Cavalheiro; Dorneles, Aracélli Gnatta; Sperotto, Rita Leal; Duarte, Marta Medeiros Frescura; Schetinger, Maria Rosa Chitolina; Loro, Vania Lúcia



Changes in Cerebrospinal Fluid Cytokine Expression in Tuberculous Meningitis Patients with Treatment  

Microsoft Academic Search

Background: The prevalence of tuberculous meningitis (TBM) is very high in developing areas of the world. Inflammation and cytokine patterns produced by T lymphocytes play an important role in susceptibility to infections. The inflammatory response and production of cytokines in the cerebrospinal fluid (CSF) of patients with TBM are well documented. Conversely, little is known about the role of pro-

Rajpal S. Kashyap; Poonam S. Deshpande; Sonali R. Ramteke; Milind S. Panchbhai; Hemant J. Purohit; Girdhar M. Taori; Hatim F. Daginawala



Value of cerebrospinal fluid examination in the diagnosis of meningitis in the newborn  

Microsoft Academic Search

Between 1 October 1988 and 30 September 1991 the results of all 896 cerebrospinal fluid examinations from 736 neonates were correlated with clinical diagnosis, treatment, and outcome. The prevalence of fungal or bacterial meningitis in babies requiring lumbar puncture was only 0.95%. Gram staining had a sensitivity of 68% and a positive predictive value of only 46% for the diagnosis

L Hristeva; I Bowler; R Booy; A King; A R Wilkinson



Cerebrospinal fluid flow abnormalities in patients with neoplastic meningitis. An evaluation using /sup 111/In-DTPA ventriculography  

SciTech Connect

Cerebrospinal fluid flow dynamics were evaluated by /sup 111/In-diethylenetriamine pentaacetic acid (/sup 111/In-DTPA) ventriculography in 27 patients with neoplastic meningitis. Nineteen patients (70 percent) had evidence of cerebrospinal fluid flow disturbances. These occurred as ventricular outlet obstructions, abnormalities of flow in the spinal canal, or flow distrubances over the cortical convexities. Tumor histology, physical examination, cerebrospinal fluid analysis, myelograms, and computerized axial tomographic scans were not sufficient to predict cerebrospinal fluid flow patterns. These data indicate that cerebrospinal fluid flow abnormalities are common in patients with neoplastic meningitis and that /sup 111/In-DTPA cerebrospinal fluid flow imaging is useful in characterizing these abnormalities. This technique provides insight into the distribution of intraventricularly administered chemotherapy and may provide explanations for treatment failure and drug-induced neurotoxicity in patients with neoplastic meningitis.

Grossman, S.A.; Trump, D.L.; Chen, D.C.; Thompson, G.; Camargo, E.E.



Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis  

Microsoft Academic Search

BackgroundAdjunctive dexamethasone reduces mortality from tuberculous meningitis, but how it produces this effect is not known. Matrix metalloproteinases (MMPs) are important in the immunopathology of many inflammatory CNS diseases thus we hypothesized that that their secretion is important in TBM and might be influenced by dexamethasone.Methodology\\/Principal FindingsThe kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations

Justin A. Green; Chau T. H. Tran; Jeremy J. Farrar; Mai T. H. Nguyen; Phu H. Nguyen; Sinh X. Dinh; Nghia D. T. Ho; Chuong V. Ly; Hien T. Tran; Jon S. Friedland; Guy E. Thwaites



Oxidative Stress in Cerebrospinal Fluid of Patients with Aseptic and Bacterial Meningitis  

Microsoft Academic Search

This study aimed to determine whether patients with aseptic and bacterial meningitis presented alterations in oxidative stress\\u000a parameters of cerebrospinal fluid (CSF). A total of 30 patients were used in the research. The CSF oxidative stress status\\u000a has been evaluated through many parameters, such as lipid peroxidation through thiobarbituric acid reactive substances (TBARS)\\u000a and antioxidant defense systems such as superoxide

Charlene Cavalheiro de Menezes; Aracélli Gnatta Dorneles; Rita Leal Sperotto; Marta Medeiros Frescura Duarte; Maria Rosa Chitolina Schetinger; Vania Lúcia Loro



Cerebrospinal fluid C-reactive protein in the laboratory diagnosis of bacterial meningitis.  


Samples of cerebrospinal fluid from 112 cases of suspected meningitis were tested for the presence of C-reactive protein (CRP), using a qualitative and quantitative slide test. Bacterial meningitis was confirmed in 34 patients, based on CSF and blood culture results, and/or elevated CSF white blood cell (WBC) count and typical biochemical profile. There were 8 patients with early onset, and 3 who had received prior antimicrobial therapy among the 5 neonates, 23 children, and 6 adults with bacterial meningitis. Organisms recovered from CSF, and/or blood, included Haemophilus influenzae 14, Streptococcus pneumoniae 9, Streptococcus group B-5, Staphylococcus aureus 2, E. coli 2 and Klebsiella pneumoniae 1. Slide test was positive for CRP in 33 cases, giving a sensitivity of 97% which compared favourably with elevated CSF protein 33%, decreased CFS glucose 64.7% CSF glucose/blood glucose less than 1/2, 85%, raised CSF WBC 38.2%, raised CSF PMN 61.7%, CSF culture positive 88.2%, and CSF gram-positive 82.5%. Slide test was positive for CRP in 1 of 78 CSF samples negative for bacterial meningitis, giving a specificity of 98%. It was concluded that testing of CSF for CRP is a simple, rapid and accurate method for the laboratory diagnosis of bacterial meningitis, which is particularly appropriate for areas lacking adequate laboratory facilities. PMID:3895817

Macfarlane, D E; Narla, V R



Microscopic Examination and Broth Culture of Cerebrospinal Fluid in Diagnosis of Meningitis  

PubMed Central

We reviewed the results of microscopic Gram stain examination and routine culture for 2,635 cerebrospinal fluid (CSF) samples processed in an adult hospital microbiology laboratory during 55 months. There were 56 instances of bacterial or fungal meningitis (16 associated with central nervous system [CNS] shunt infection), four infections adjacent to the subarachnoid space, four cases of sepsis without meningitis, and an additional 220 CSF specimens with positive cultures in which the organism isolated was judged to be a contaminant. Because 121 of these contaminants were isolated in broth only, elimination of the broth culture would decrease unnecessary work. However, 25% of the meningitis associated with CNS shunts would have been missed by this practice. The most common cause of meningitis was Cryptococcus neoformans, followed by Streptococcus pneumoniae and Neisseria meningitidis. In 48 of 56 (88%) of cases, examination of the Gram-stained specimen revealed the causative organism. If patients who had received effective antimicrobial therapy prior to lumbar puncture are excluded, the CSF Gram stain is 92% sensitive. Microscopic examination incorrectly suggested the presence of organisms in only 3 of 2,635 (0.1%) CSF examinations. Thus, microscopic examination of Gram-stained, concentrated CSF is highly sensitive and specific in early diagnosis of bacterial or fungal meningitis.

Dunbar, Sherry A.; Eason, Rachel A.; Musher, Daniel M.; Clarridge, Jill E.



Predictive Value of Serum and Cerebrospinal Fluid Procalcitonin Levels for the Diagnosis of Bacterial Meningitis  

Microsoft Academic Search

Background: The value of serum and cerebrospinal fluid (CSF) procalcitonin for differentiating between acute bacterial and viral meningitis\\u000a was assessed and compared to other parameters which are usually used in clinical practice.\\u000a \\u000a \\u000a \\u000a \\u000a Patients: 45 adult patients (20 with bacterial and 25 with tick-borne encephalitis, TBE) were included in this prospective study.\\u000a \\u000a \\u000a \\u000a \\u000a Results: The median serum procalcitonin level in patients with

M. Jereb; I. Muzlovic; S. Hojker; F. Strle



Two dimensional difference gel electrophoresis analysis of cerebrospinal fluid in tuberculous meningitis patients.  


Tuberculous meningitis (TBM) is a serious complication of tuberculosis that affects the central nervous system. Present methods to diagnose TBM are not suitable for early diagnosis. Molecular markers and sensitive methods to identify them in the early stage of infection of TBM are critically needed for efficient management. We have done the proteomic analysis of TBM cerebrospinal fluid (n=20) with 2-dimensional difference gel electrophoresis (2D-DIGE) and mass spectrometry. We identified 11 human proteins and 8 mycobacterial proteins with changed expression levels in comparison to controls. Arachidonate 5-lipoxygenase and glial fibrillary acidic protein, two of the identified proteins, were validated with western blot technique on a larger set of disease and control samples (n=40). These two proteins were also analyzed in fungal meningitis samples. We suggest that arachidonate 5-lipoxygenase can be considered for validation as a potential marker for diagnosis of TBM. PMID:21723968

Kataria, Jitender; Rukmangadachar, Lokesh A; Hariprasad, Gururao; O, Jithesh; Tripathi, Manjari; Srinivasan, Alagiri



Adhesion molecule levels in serum and cerebrospinal fluid in children with bacterial meningitis and sepsis  

PubMed Central

Background: Adhesion molecules play a role in leukocyte recruitment during central nervous system (CNS) inflammation. Aim: This study was designed to compare serum, cerebrospinal fluid (CSF) concentrations of adhesion molecules in children with meningitis and sepsis, and to evaluate their sources. Setting: This study was carried out at Pediatric Department, King Abdulaziz University Hospital from January 2007 to June 2008. Design: Serum and CSF samples were collected on admission from meningitis (n = 40), sepsis (n = 20) patients, and sera from controls (n = 20). Materials and Methods: Endothelial (E), leukocyte (L), platelet (P) selectins intercellular cell adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecules-1 (VCAM-1) were measured using ELISA. Statistics: ANOVA and Spearman's correlations were used. Adhesion molecules with albumin concentration were estimated in CSF/serum to calculate concentration quotients. Results: In meningitis, serum sE-, sL-, sP-selectins sICAM-1, sVCAM-1 levels were higher than controls. Compared to sepsis, serum sE-selectin, sL-selectin, sVCAM-1, CSF-sL-selectin, CSF-sVCAM-1, VCAM-1 ratio and index were higher, while serum sP-selectin was lower than meningitis. sE-selectin ratio, CSF sICAM-1 were higher in meningitis with positive than negative culture. The sE-selectin index was higher in meningitis with neurological complication than those without it. In meningitis, correlation was found between CSF protein and CSF white blood cell counts (WBCs), CSF sICAM-1, CSF sVCAM-1 and between CSF sE-selectin and CSF sICAM-1. Conclusions: This study supports the role of adhesion molecules especially sL-selectin, sVCAM-1 in meningitis and suggests further research to determine their use as biomarkers for meningitis and use of their antagonists as therapeutic for CNS inflammation. The presence of discrepancy of CSF/serum ratios for molecules of same molecular weight suggest intrathecal shedding in addition to diffusion through the blood-CSF barrier.

Jaber, Soad M.; Hamed, Enas A.; Hamed, Sherifa A.



rmpM Genosensor for Detection of Human Brain Bacterial Meningitis in Cerebrospinal Fluid.  


Human brain bacterial meningitis is a life-threatening disease caused mainly by Neisseria meningitidis, lead to damage of the outer membrane covering (meninges) of brain or even death. The usual methods of diagnosis are either time-consuming or have some limitations. The specific rmpM (reduction-modifiable protein M) virulent gene based genosensor is more sensitive, specific, and can detect N. meningitidis directly from the patient cerebrospinal fluid in 30 min including 1-min response time. 5'-Thiol-labeled single-stranded DNA (ssDNA) probe was immobilized onto screen-printed gold electrode (SPGE) and hybridized with denatured (95 °C) single-stranded genomic DNA (ssG-DNA) for 10 min at 25 °C. The electrochemical response was measured by cyclic voltammetry, differential pulse voltammetry (DPV) and electrochemical impedance using redox indicators. The sensitivity of the genosensor was 9.5087?(?A/cm(2))/ng with DPV and limit of detection was 3 ng/6 ?L ssG-DNA. The immobilization of the ssDNA probe and hybridization with ssG-DNA from N. meningitidis was characterized by atomic force microscopy and Fourier transform infrared spectroscopy. The rmpM genosensor was stable for 6 months at 4 °C with 10 % loss in initial DPV current. The advantage of rmpM genosensor is to detect bacterial meningitis simultaneously in multiple patients using SPGE array during an outbreak of the disease. PMID:23824531

Dash, Sandip Kumar; Sharma, Minakshi; Khare, Shashi; Kumar, Ashok



Genetic Variation and Cerebrospinal Fluid Levels of Mannose Binding Lectin in Pneumococcal Meningitis Patients  

PubMed Central

It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05–64.1; p?=?0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39–3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis.

Brouwer, Matthijs C.; Baas, Frank; van der Ende, Arie; van de Beek, Diederik



Genetic variation and cerebrospinal fluid levels of mannose binding lectin in pneumococcal meningitis patients.  


It has been suggested that genetic variants in mannose binding lectin (MBL2) influence susceptibility and outcome of invasive pneumococcal disease. We assessed the influence of genetic variation in MBL2 on susceptibility, outcome and causative serotype of pneumococcal meningitis in a prospective nationwide cohort study including 299 white patients and 216 controls. We assessed functionality of the genetic polymorphisms by measuring levels of MBL, C3a, iC3b, C5a and sC5b-9 in cerebrospinal fluid. We also performed a meta-analysis of studies on MBL2 polymorphisms and susceptibility to invasive pneumococcal disease. The risk of contracting pneumococcal meningitis was substantially increased for white individuals homozygous with the defective MBL2 0/0 genotype (odds ratio [OR] 8.21, 95% confidence interval [CI] 1.05-64.1; p?=?0.017). CSF MBL levels were significantly lower in patients with the A/0 and 0/0 genotype compared to homozygotes for the wild-type alleles (A/A; p<0.001). CSF MBL levels were positively correlated with C3a and iC3b levels, indicating complement activation by the lectin pathway. The effect of MBL2 genetic variants on susceptibility remained robust in a meta-analysis including 5 studies with 287 patients (OR 2.33, 99% CI 1.39-3.90). We conclude that MBL2 polymorphisms influence CSF MBL levels and substantially increase the risk of pneumococcal meningitis. PMID:23741476

Brouwer, Matthijs C; Baas, Frank; van der Ende, Arie; van de Beek, Diederik



Cerebrospinal Fluid (1,3)-?-d-Glucan Detection as an Aid for Diagnosis of Iatrogenic Fungal Meningitis  

PubMed Central

This case series highlights our experience with use of the Fungitell assay for quantifying (1,3)-?-d-glucan in cerebrospinal fluid during the current U.S. outbreak of fungal meningitis related to contaminated methylprednisolone acetate. This test may prove a useful adjunct in diagnosis and management of exposed patients.

Lyons, Jennifer L.; Roos, Karen L.; Marr, Kieren A.; Neumann, Henry; Trivedi, Julie B.; Kimbrough, Dorlan J.; Steiner, Lisa; Thakur, Kiran T.; Harrison, Daniel M.



Morphological indications for considerable diffuse reabsorption of cerebrospinal fluid in spinal meninges particularly in the areas of meningeal funnels. An electronmicroscopical study including tracing experiments in rats.  


Transmission and scanning electron microscopical observations in the rat indicate a considerable capacity of the spinal meninges to reabsorb cerebrospinal fluid. The density of blood vessels and lymphatics in the duramater is extremely high, particularly in the areas of meningeal funnels and spinal nerve root sleeves. Arterioles with closely related unmyelinated nerve fibres, many fenestrated capillaries and venules predetermine these areas as sites where absorption processes could take place. At certain sites of the meningeal angle region, the arachnoid membrane, mostly multilayered, is reduced to only three or four layers. Intercellular discontinuities and cytoplasmic fenestrations occurring in the arachnoid lining cell layer result in direct communications between the subarachnoid space and cisterns of the arachnoid "reticular layer". These cisterns are partly fluid-filled, partly occupied by a net of collagen fibre bundles. Some cisterns harbour macrophages that often project filiform processes through the lining cell layer into the subarachnoid space, contacting cerebrospinal fluid. Desmosomes and gap junctions are present in all layers of the arachnoid. However, tight junctions and the continuous electrondense intercellular gap, known to occur normally within the "arachnoid barrier layer", were not seen in many sites of the meningeal angle region. Numerous arachnoid cells display a high degree of vesiculation. Cationized ferritin, introduced in vivo into the rat subarachnoid space, passes inter- and intracellularly from the cerebrospinal fluid compartment through the arachnoid membrane, reaching dural blood vessels and lymphatics. Tracer could be visualized both in the cytoplasm of the endothelium and on the luminal surface of the cells. Tracer also passed through pial cell layers into pial vessels, through leptomeningeal sheaths into vessels crossing the subarachnoid space, into the connective tissue compartment and into vessels of spinal dorsal root ganglia. In the angle region, a particularly large number of macrophages can be found on the surface of leptomeninges, within the arachnoid reticular layers, and in close relation to dural and epidural capillaries, venules and lymphatics. Their possible role in the process of cerebrospinal fluid reabsorption is discussed. PMID:8042766

Zenker, W; Bankoul, S; Braun, J S



Lack of value of routine analysis of cerebrospinal fluid for prediction and diagnosis of external drainage-related bacterial meningitis  

Microsoft Academic Search

OBJECT: Routine microbiological and chemical analysis of cerebrospinal fluid (CSF) is often performed to diagnose external drainage-related bacterial meningitis (ED-BM) at an early stage. A cohort study was performed to investigate the value of several commonly used CSF parameters for the prediction and diagnosis of ED-BM. METHODS: In a cohort of 230 consecutive patients in whom external drains had been

Rogier P. Schade; Janke Schinkel; Freek W. C. Roelandse; Ronald B. Geskus; Leo G. Visser; Marc C. van Dijk; Joan H. C. Voormolen; Hans van Pelt; Ed J. Kuijper



Cerebrospinal Fluid Leakage During Transsphenoidal Surgery: Postoperative External Lumbar Drainage Reduces the Risk for Meningitis  

Microsoft Academic Search

Postoperative meningitis is a well known complication of transsphenoidal surgery (TSS). The objective of this study was to\\u000a evaluate whether postoperative external cerobrospinal fluid (CSF) drainage in case of intraoperative CSF-leakage, reduces\\u000a the risk of postoperative meningitis. We retrospectively reviewed a series of 278 consecutive transsphenoidal operations.\\u000a In all operations with intraoperative CSF leakage, an external lumbar drain (ELD) was

M. O. van Aken; R. A. Feelders; S. de Marie; J. H. van de Berge; A. H. G. Dallenga; E. J. Delwel; R. M. L. Poublon; J. A. Romijn; A. J. van der Lely; S. W. J. Lamberts; W. W. de Herder



Passage of cefotaxime and ceftriaxone into cerebrospinal fluid of patients with uninflamed meninges.  

PubMed Central

Cefotaxime and ceftriaxone have proven to be effective in pyogenic infections of the central nervous system. Since in some bacterial central nervous system infections the blood-cerebrospinal fluid (CSF) barrier is either minimally impaired or recovers in the course of the illness, we studied the penetration of both antibiotics in the absence of inflamed meninges. Patients who had undergone external ventriculostomies for noninflammatory occlusive hydrocephalus received either cefotaxime (2 g/30 min) or ceftriaxone (2 g/30 min) to treat extracerebral infections. Serum and CSF were drawn repeatedly after the first dose. With ceftriaxone, they were also drawn after the last dose. The concentrations of cefotaxime, its metabolite desacetylcefotaxime, and ceftriaxone were determined by high-performance liquid chromatography with UV detection. Maximum concentrations of cefotaxime in CSF were reached 0.5 to 8 h (median = 3 h; n = 6) after the end of the infusion and ranged from 0.14 to 1.81 mg/liter (median = 0.44 mg/liter; n = 6). Maximum levels of ceftriaxone in CSF ranging from 0.18 to 1.04 mg/liter (median = 0.43 mg/liter; n = 5) were seen 1 to 16 h (median = 12 h; n = 5) after the infusion. The elimination half-life of cefotaxime in CSF was 5.0 to 26.9 h (median = 9.3 h; n = 5), and that of ceftriaxone was 15.7 to 18.4 h (median = 16.8 h; n = 3). It is concluded that after a single dose of 2 g, maximal concentrations of cefotaxime and ceftriaxone in CSF do not differ substantially. The long elimination half-lives guarantee uniform concentrations in CSF. These concentrations reliably inhibit highly susceptible bacteria but cannot be relied on to inhibit staphylococci and penicillin G-resistant Streptococcus pneumoniae.

Nau, R; Prange, H W; Muth, P; Mahr, G; Menck, S; Kolenda, H; Sorgel, F



The Causative Pathogen Determines the Inflammatory Profile in Cerebrospinal Fluid and Outcome in Patients with Bacterial Meningitis  

PubMed Central

Background. The brain's inflammatory response to the infecting pathogen determines the outcome of bacterial meningitis (BM), for example, the associated mortality and the extent of brain injury. The inflammatory cascade is initiated by the presence of bacteria in the cerebrospinal fluid (CSF) activating resident immune cells and leading to the influx of blood derived leukocytes. To elucidate the pathomechanisms behind the observed difference in outcome between different pathogens, we compared the inflammatory profile in the CSF of patients with BM caused by Streptococcus pneumonia (n = 14), Neisseria meningitidis (n = 22), and Haemophilus influenza (n = 9). Methods. CSF inflammatory parameters, including cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were assessed in a cohort of patients with BM from Burkina Faso. Results. Pneumococcal meningitis was associated with significantly higher CSF concentrations of IFN-?, MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a fatal outcome, levels of TNF-?, IL-1?, IL-1RA, IL-6, and TGF-? were significantly higher. Conclusion. The signature of pro- and anti-inflammatory mediators and the intensity of inflammatory processes in CSF are determined by the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis being associated with a higher case fatality rate than meningitis caused by N. meningitidis or H. influenzae.

Grandgirard, Denis; Gaumann, Rahel; Coulibaly, Boubacar; Dangy, Jean-Pierre; Sie, Ali; Junghanss, Thomas; Schudel, Hans; Pluschke, Gerd; Leib, Stephen L.



IgG antibody to Mycobacterium tuberculosis antigen-5 in cerebrospinal fluid and its diagnostic application in tuberculous meningitis.  


IgG antibody to M. tuberculosis antigen-5 was detected by non-competitive ELISA in cerebrospinal fluid specimens (CSF), from 40 patients with clinical diagnosis of tuberculous meningitis and in 42 patients of non-tuberculous neurological diseases. The geometric mean antibody titer in CSF specimen for tuberculous and non-tuberculous groups were 156 and 8 respectively. The antibody titer in CSF specimens showed no correlation to IgG levels, tuberculin reactor status and duration of chemotherapy in patients with tuberculous meningitis. At a dilution end-point 1:40, the assay had a sensitivity of 84% and specificity of 92%. However at dilution end-point 1:80, the specificity of the assay could be increased to 100% but sensitivity of the assay decreased to 75%. IgG antibody detection against M. tuberculosis antigen-5 by non-competitive ELISA, described in this communication has potential application in the laboratory diagnosis of tuberculous meningitis, particularly in developing countries where the incidence and prevalence of tuberculous meningitis is still high. In culture-negative cases of tuberculous meningitis, non-competitive ELISA could be applied as an alternative diagnostic tool. PMID:2126255

Mathai, A; Radhakrishnan, V V; Sehgal, S



Variables that influence HIV1 cerebrospinal fluid viral load in cryptococcal meningitis: a linear regression analysis  

Microsoft Academic Search

BACKGROUND: The central nervous system is considered a sanctuary site for HIV-1 replication. Variables associated with HIV cerebrospinal fluid (CSF) viral load in the context of opportunistic CNS infections are poorly understood. Our objective was to evaluate the relation between: (1) CSF HIV-1 viral load and CSF cytological and biochemical characteristics (leukocyte count, protein concentration, cryptococcal antigen titer); (2) CSF

Diego M Cecchini; Ana M Cañizal; Haroldo Rojas; Alicia Arechavala; Ricardo Negroni; María B Bouzas; Jorge A Benetucci



Genomic Comparison of Escherichia coli K1 Strains Isolated from the Cerebrospinal Fluid of Patients with Meningitis  

PubMed Central

Escherichia coli is a major cause of enteric/diarrheal diseases, urinary tract infections, and sepsis. E. coli K1 is the leading gram-negative organism causing neonatal meningitis, but the microbial basis of E. coli K1 meningitis is incompletely understood. Here we employed comparative genomic hybridization to investigate 11 strains of E. coli K1 isolated from the cerebrospinal fluid (CSF) of patients with meningitis. These 11 strains cover the majority of common O serotypes in E. coli K1 isolates from CSF. Our data demonstrated that these 11 strains of E. coli K1 can be categorized into two groups based on their profile for putative virulence factors, lipoproteins, proteases, and outer membrane proteins. Of interest, we showed that some open reading frames (ORFs) encoding the type III secretion system apparatus were found in group 2 strains but not in group 1 strains, while ORFs encoding the general secretory pathway are predominant in group 1 strains. These findings suggest that E. coli K1 strains isolated from CSF can be divided into two groups and these two groups of E. coli K1 may utilize different mechanisms to induce meningitis.

Yao, Yufeng; Xie, Yi; Kim, Kwang Sik



Sensitivity andSpecificity ofEnzyme-Linked Immunosorbent Assay intheDetection ofAntigen inTuberculous Meningitis Cerebrospinal Fluids  

Microsoft Academic Search

A sandwich enzyme-linked immunosorbent assaywasdeveloped foritspotential utility inthedetection of antigen inthecerebrospinal fluid ofpatients withtuberculous meningitis. Cerebrospinal fluids examined included those fromuhtreated (group Ia)andtreated (group lb)Mycobacterium tuberculosis meningitis, nonseptic central nervous conditions (groupH1)suchas epilepsy, viralmeningitis, andtetany, and nonmycobacterial septic meningitis (group III). Theaveragelevels ofantigens determined andpercent positive specimens, respectively, foreachgroupwere(group): Ia,1.8,ug\\/ml and75%positive; Ib,0.37,ug\\/ml and36% positive; II,:0.036 ,ug\\/ml and100%negative; andIII,0.075 ,ug\\/ml and100%negative.




Changes of cerebrospinal fluid tumor marker levels may predict response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer  

Microsoft Academic Search

The aim of the present study was to evaluate the predictive value of cerebrospinal fluid (CSF) tumor marker levels in patients\\u000a with breast cancer and carcinomatous meningitis. Serial CSF and serum tumor marker (CEA, CA-15.3, CA-125, and CA-19.9) measurements\\u000a were performed in five patients with breast cancer developing carcinomatous meningitis in an attempt to correlate these with\\u000a clinical outcome under

Christos Kosmas; Nicolas B. Tsavaris; Georgia Soukouli; Panagiotis Gouveris; George Tsakonas; John Katselis; Heraklis Alexopoulos; Nicolas Mylonakis; Athanasios Karabelis



Determination of bacterial meningitis: a retrospective study of 80 cerebrospinal fluid specimens evaluated by four in vitro methods.  


A total of 80 cerebrospinal fluid specimens were analyzed for bacterial meningitis by four procedures readily available to most laboratories. These tests included routine culturing. Gram staining, countercurrent immunoelectrophoresis, staphylococcal coagglutination (CoA) with laboratory-prepared reagents, and CoA with Pharmacia Diagnostics reagents. A total of 56 specimens were positive for bacterial agents by routine culturing: Gram stain results were positive for 64% of all specimens positive by culturing. For 36 specimens from patients with suspected meningitis due to either Haemophilus influenzae type b, Streptococcus pneumoniae, or group B streptococci, detection was 97% with Pharmacia CoA reagents, 94% with laboratory-prepared CoA reagents, 89% with routine culturing, 78% with countercurrent immunoelectrophoresis, and 75% with Gram staining. One specimen which contained Klebsiella pneumoniae was false positive for S. pneumoniae in tests with both of the CoA reagents and in countercurrent immunoelectrophoresis. A Gram stain of this specimen clearly showed gram-negative bacilli, which were confirmed by culturing. Although a positive culture and a positive Gram stain are definitive evidence of bacterial meningitis, rapid immunological tests can provide valuable clinical information as an adjunct to culture and Gram stain results. Serological tests with Pharmacia CoA reagents produced more positive results than either laboratory-prepared CoA reagents or countercurrent immunoelectrophoresis. PMID:6752193

Wasilauskas, B L; Hampton, K D



An iTRAQ approach to quantitative proteome analysis of cerebrospinal fluid from patients with tuberculous meningitis.  


To study the cerebrospinal fluid (CSF) protein profiles of tuberculous meningitis (TBM) and discover potential biomarkers for TBM, differential expression of proteins in the CSF of patients with TBM, patients with cryptococcal meningitis, and a control group were compared using isobaric tags for relative and absolute quantitation labelling (iTRAQ) coupled with 2-dimensional liquid chromatography-tandem mass spectrometry (LC-MS). As a result, a total of 208 unique proteins with a molecular weight ranging from 10 KD to 135 KD were identified and quantified in CSF samples from patients with TBM. Of the proteins, 9 were expressed at levels differing 2.0 fold, 6 were up-regulated, and 3 were down-regulated. These proteins appear to be involved in calcium ion binding, lipoprotein metabolism, immune response, and signal conduction. Two differentially expressed proteins were identified using ELISA. The present study represents the successful use of iTRAQ to examine CSF from patients with TBM. The differentially expressed proteins identified may be potential diagnostic biomarkers and provide valuable insight into the underlying mechanisms of TBM. This study also demonstrated that the differential protein profiles of diseases can be quickly determined using iTRAQ-LC-MS, a potential method for quantitative comparative proteomics. PMID:24056169

Ou, Q; Liu, X H; Cheng, X J



Isolation of toscana virus from the cerebrospinal fluid of a man with meningitis in marseille, france, 2010.  


Abstract Toscana virus (TOSV; Bunyaviridae, Phlebovirus) is an emerging arthropod-borne virus transmitted by phlebotomine sandflies. TOSV is a frequent cause of central nervous system infection during the warm season in several countries bordering the Mediterranean Sea. Here, we report a case of TOSV aseptic meningitis diagnosed in 2012 in Marseille, France. The virus strain was recovered in cell culture from the cerebrospinal fluid. New-generation sequencing based on Ion Torrent technology was used to determine its complete genome sequence. Phylogenetic analysis based on the partial L segment revealed that this isolate belongs to the lineage B together with other French, Spanish, and Moroccan strains. Although several cases of TOSV meningitis are reported in the literature, few of them are diagnosed by RT-PCR combined with virus isolation and further sequence characterization. This case report supports that virus isolation should be attempted whenever possible because this remains the gold standard technique for diagnosis of arthropod-borne viral infections. PMID:23808972

Nougairede, Antoine; Bichaud, Laurence; Thiberville, Simon-Djamel; Ninove, Laetitia; Zandotti, Christine; de Lamballerie, Xavier; Brouqui, Philippe; Charrel, Remi N



Low levels of LTB4 in cerebrospinal fluid of AIDS patients with cryptococcal meningitis.  


In this study we evaluated the release of leukotriene B4 (LTB4) in the cerebrospinal fluid (CSF) of 12 patients with Acquired Immunodeficiency Syndrome (AIDS), which disease was complicated by Cryptococcal Meninigitis and in CSF of 12 control subjects with inflammatory and degenerative pathologies of the Central Nervous System (CNS). We obtained low levels of LTB4 in all the AIDS patients (mean 60.5 pg/ml), while the HIV negative subjects with degenerative and inflammatory pathologies of CNS showed a mean of 91.5 pg/ml. The finding of low levels of this inflammatory reaction mediator agrees with the limited clinical symptoms of cryptococcal meningoencephalitis in patients affected by AIDS. PMID:8735435

Froldi, M; Parma, M; Marenzi, R; Piona, A; Lorini, M; Nobile Orazio, E; Castagna, A; Lazzarin, A



In vitro killing activities of antibiotics at clinically achievable concentrations in cerebrospinal fluid against penicillin-resistant Streptococcus pneumoniae isolated from children with meningitis.  

PubMed Central

We evaluated the in vitro killing activities of ceftriaxone, imipenem, vancomycin, gentamicin, fosfomycin, and rifampin, alone and in combination, against 26 Streptococcus pneumoniae strains (penicillin G MICs, > 0.125 to 2 micrograms/ml) isolated from the cerebrospinal fluid of children with meningitis. The antibiotics were tested at clinically achievable concentrations in cerebrospinal fluid. After 5 h of incubation, imipenem was the most effective drug. None of the combinations had synergistic activity. Killing by beta-lactam antibiotics or vancomycin was enhanced by the addition of gentamicin, reduced by the addition of rifampin, and unaffected by the addition of fosfomycin.

Doit, C P; Bonacorsi, S P; Fremaux, A J; Sissia, G; Cohen, R; Geslin, P L; Bingen, E H



Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early diagnosis of tuberculosis meningitis.  

PubMed Central

A number of different biochemical and serological tests have been described recently for the early and accurate diagnosis of tuberculous meningitis. None of these tests has yet gained widespread acceptance in clinical medicine or in microbiology laboratories. To investigate this problem we evaluated adenosine deaminase activity (ADA), an enzyme linked immunosorbent assay (ELISA) that detects antibody to antigen 5 of Mycobacterium tuberculosis, and the radioactive bromide partition test (BPT) in the cerebrospinal fluid (CSF). Cerebrospinal fluid specimens from children with tuberculous, pyogenic, and viral meningitis as well as from patients with pulmonary tuberculosis without meningitis and from controls with normal CSFs were included inn the study. In addition, we estimated ADAs in serum samples from selected children in these groups. The sensitivity and specificity of the three tests evaluated in the CSF were: ADA assay 73% and 71%; BPT 92% and 92%; and ELISA for antibody to antigen 5, 53% and 90%, 40% and 94%, and 27% and 100%, respectively, at tires of more than or equal to 1:20, 1:40, and 1:80. The serum ADA was lower (11.0 +/- 6.15 IU/l) in children with tuberculous meningitis when compared with those with pulmonary tuberculosis alone (25.8 +/- 20.9 IU/l). The BPT was found to be the most reliable test in the early differentiation of tuberculous from other causes of meningitis and remained abnormal for a period of up to five months after the beginning of treatment. Accordingly, we believe that the BPT should be used in conjunction with bacterial and fungal antigen detection systems for the initial differentiation of clinically suspicious tuberculous meningitis from Gram or culture negative cases, or both, of bacterial and fungal meningitis.

Coovadia, Y M; Dawood, A; Ellis, M E; Coovadia, H M; Daniel, T M



Assessment of free light chains in the cerebrospinal fluid of patients with lymphomatous meningitis - a pilot study  

PubMed Central

Background Lymphomatous meningitis (LM) represents a severe complication of malignant lymphomas. While clinical suspicion is raised by symptoms ranging from mild disturbances of sensation to severe pain or impaired consciousness, the definite diagnosis of LM is often difficult to obtain. Since B-cell lymphomas are clonally restricted to express either kappa or lambda immunoglobulin light chain, we hypothesised that analysis of free light chain (FLC) ratios might facilitate the diagnosis of LM. Methods Kappa and lambda FLC were measured using a novel nephelometric assay in cerebrospinal fluid (CSF) and serum from 17 patients. 5/17 suffered from LM as demonstrated by cytology, immunocytology, and/or imaging procedures. Results Measurement of FLC concentrations in CSF was achieved for all 17 patients. FLC levels in CSF were lower than serum FLC levels in samples for the same patient obtained at the same time (p < 0.01). CSF and serum FLC concentrations correlated weakly in all patients irrespective of LM status. Significantly more patients with cytopathologically and immunohistochemically proven LM displayed abnormal kappa/lambda FLC ratios in CSF compared to individuals with no LM (p < 0.01). Conclusion This is the first report demonstrating that a significant proportion of LM patients display an abnormal kappa/lambda FLC ratio in the CSF.

Hildebrandt, B; Muller, C; Pezzutto, A; Daniel, PT; Dorken, B; Scholz, C



Levels of three inflammation markers, C-reactive protein, serum amyloid A protein and procalcitonin, in the serum and cerebrospinal fluid of patients with meningitis.  


The levels of C-reactive protein (CRP) and serum amyloid A protein (SAA) in blood are increased in patients with inflammatory diseases as acute phase proteins. Most of the presently used indicators of inflammation, such as body temperature, white cell count, erythrocyte sedimentation rate or CRP, are non-specific parameters. In contrast, procalcitonin (PCT) has been reported to be selectively induced by severe bacterial infection during the systemic inflammatory response syndrome (SIRS), and also in sepsis or multiorgan dysfunction syndrome. PCT expression is only slightly induced, if at all, by viral infections, autoimmune disorders, neoplastic diseases and trauma of surgical intervention. We measured the concentrations of CRP, SAA and PCT in the sera and cerebrospinal fluid (CSF) of 30 patients with bacterial, viral, or mycotic meningitis, and 12 patients with a noninflammatory central nervous system disease as controls. An extremely high CRP level in CSF of above 100 microg/L was seen in all seven bacterial meningitis patients and in only 10% of the viral meningitis patients. A high SAA level in CSF of greater than 10 microg/L was observed in all of the bacterial meningitis and mycotic meningitis patients, and in 95% of the viral meningitis patients. Among those with bacterial meningitis, the serum PCT level was more elevated in those with more serious bacterial meningitis. The PCT level in the CSF did not significantly differ among the patients with the three types of meningitis. However, the serum PCT level was very high above 0.1 microg/L in all seven bacterial meningitis patients, especially in the clinically serious cases. PMID:11763415

Shimetani, N; Shimetani, K; Mori, M



Cerebrospinal Fluid and Serum Concentrations of Rifampin in Meningeal Tuberculosis after Intravenous Administration,  

National Technical Information Service (NTIS)

Rifampin given orally was found to cross the blood-brain barrier, and was comparable to ethamputol in the treatment of tuberculous meningitis. Due to the difficulty of administering oral therapy, as most of the patients are unable to swallow properly, int...

I. A. Mikhail N. I. Girgis A. L. Bourgeois C. R. Lissner



Predominance of Vgamma9/Vdelta2 T lymphocytes in the cerebrospinal fluid of children with tuberculous meningitis: reversal after chemotherapy.  

PubMed Central

BACKGROUND: We analyzed the gammadelta T cell composition and responses in the peripheral blood and cerebrospinal fluid (CSF) of children affected by tuberculous meningitis (TBM) and in control children. MATERIALS AND METHODS: Peripheral blood and CSF samples were stimulated with different phosphoantigens and IL-2, and expansion of Vgamma9/Vdelta2 T cells assessed by FACS analysis. Vgamma9/Vdelta2 lines were obtained by culturing CSF or peripheral blood mononuclear cells (PBMC) in vitro with phosphoantigens and IL-2 for 2 months, and tested for proliferation and cytokine production in response to phosphoantigens. Vdelta2(D)Jdelta junctional sequence length was assessed by PCR. RESULTS: The repertoire of gammadelta T cells from the CSF of TBM patients was characterized by the predominance of Vgamma9/Vdelta2 T lymphocytes, which accounted for >80% of gammadelta T cells. Vgamma9/Vdelta2 cells from the CSF of TBM children responded to different synthetic and natural (mycobacterial) phosphoantigens and produced discrete amounts of IFN-gamma and TNF-alpha. The in vitro expansion of Vgamma9/Vdelta2 T cells from CSF and peripheral blood of TBM patients prominently decreased following chemotherapy, and similarly, the proportion of ex vivo unstimulated Vgamma9/Vdelta2 T cells in CSF of TBM patients decreased to levels detected in the CSF of control subjects. Vdelta2 CDR3 TCR analysis showed that the remaining Vdelta2 cells in the CSF of TBM patients were still polyclonal. CONCLUSIONS: These findings are consistent with an involvement of Vgamma9/Vdelta2 T cells in TBM. http://link. html Images Fig. 3

Dieli, F.; Sireci, G.; Di Sano, C.; Champagne, E.; FourniA?, J. J.; Salerno, J. I.



Cerebrospinal fluid cytology diagnosis of meningeal carcinomatosis in patients with small-cell carcinoma of the lung. A study of interobserver and intraobserver variability.  


The interobserver and intraobserver variation in the cytologic diagnosis of malignancy was determined in 62 cerebrospinal fluid (CSF) specimens from 46 patients with small-cell carcinoma of the lung. In all patients, lumbar puncture was carried out because of suspected central nervous system metastases. Forty CSF specimens from 26 patients with meningeal carcinomatosis and thus with a high probability of a positive CSF cytology were mixed with 22 specimens from 20 patients without meningeal carcinomatosis. The slides were evaluated blindly by two observers, one of whom evaluated all specimens on two separate occasions; only positive, negative and suspicious conclusions were permitted. The consistency of the intraobserver and interobserver conclusions on the initial CSF specimen in each case was 87%. In 13% of the initial CSF specimens in each case, a suspicious conclusion was reached in one of the three evaluations. For all 62 CSFs, the intraobserver and interobserver disagreement was 2% and 3%, respectively. In the first and second evaluations by the one observer and the single evaluation by the other, 17 (65%), 15 (58%) and 12 (46%), respectively, of the 26 "high probability" patients were found to have malignant cells in the CSF. CSF cytology was negative in all 20 patients without meningeal carcinomatosis. Of 10 patients with autopsy-proven meningeal carcinomatosis, 40% were not diagnosed while alive. Multiple CSFs from repeated lumbar punctures increased the number of positive evaluations by 30%. At least 60% of those patients with a suspicious CSF cytology did in fact have meningeal carcinomatosis. On the other hand, 30% of the patients with a positive lumbar puncture had a subsequent negative one. PMID:3024430

Pedersen, A G; Olsen, J; Nasiell, M




... Hearing loss Memory difficulty Learning disabilities Brain damage Gait problems Seizures Kidney failure Shock Death Preparing for ... puncture). The definitive diagnosis of meningitis requires an analysis of your cerebrospinal fluid (CSF), which is collected ...


Eight-Plex PCR and Liquid-Array Detection of Bacterial and Viral Pathogens in Cerebrospinal Fluid from Patients with Suspected Meningitis?  

PubMed Central

We here report on the development of a novel multiplex PCR with product detection in a Luminex 100 suspension array system. The assay covers the nine most important bacterial and viral pathogens found in Danish meningitis patients. The microorganisms include Neisseria meningitidis, Streptococcus pneumoniae, Escherichia coli, Staphylococcus aureus, Listeria monocytogenes, Streptococcus agalactiae, herpes simplex virus types 1 and 2, and varicella-zoster virus. The study was based on 1,187 samples, of which 55 were found to be positive by PCR. The assay was found to have an excellent sensitivity and an excellent specificity compared to the results of a “gold standard,” defined by routine laboratory tests, for the two most important pathogens, S. pneumoniae (95 and 99.1%, respectively) and N. meningitidis (100 and 99.7%, respectively). The method provides a valuable supplement to the traditional microscopy and culture of cerebrospinal fluid (CSF) samples in a routine diagnostic setting, and results can be available within 1 workday. The method is suitable for use for the initial screening and identification of nine important microorganisms in CSF samples from patients with suspected meningitis. Compared to microscopy and culture of CSF, this rapid and sensitive method will support physicians with the selection of the appropriate antimicrobial agents and the initiation of timely treatment in the absence of live microorganisms in the CSF.

B?ving, Mette Kusk; Pedersen, Lisbeth N?rum; M?ller, Jens Kj?lseth



The use of dried cerebrospinal fluid filter paper spots as a substrate for PCR diagnosis of the aetiology of bacterial meningitis in the Lao PDR.  


We investigated whether dried cerebrospinal fluid (CSF) conserved on filter paper can be used as a substrate for accurate PCR diagnosis of important causes of bacterial meningitis in the Lao PDR. Using mock CSF, we investigated and optimized filter paper varieties, paper punch sizes, elution volumes and quantities of DNA template to achieve sensitive and reliable detection of bacterial DNA from filter paper specimens. FTA Elute Micro Card™ (Whatman, Maidstone, UK) was the most sensitive, consistent and practical variety of filter paper. Following optimization, the lower limit of detection for Streptococcus pneumoniae from dried mock CSF spots was 14 genomic equivalents (GE)/?L (interquartile range 5.5 GE/?L) or 230 (IQR 65) colony forming units/mL. A prospective clinical evaluation for S. pneumoniae, S. suis and Neisseria meningitidis was performed. Culture and PCR performed on fresh liquid CSF from patients admitted with a clinical diagnosis of meningitis (n = 73) were compared with results derived from dried CSF spots. Four of five fresh PCR-positive CSF samples also tested PCR positive from dried CSF spots, with one patient under the limit of detection. In a retrospective study of S. pneumoniae samples (n = 20), the median (IQR; range) CSF S. pneumoniae bacterial load was 1.1 × 10(4) GE/?L (1.2 × 10(5) ; 1 to 6.1 × 10(6) DNA GE/?L). Utilizing the optimized methodology, we estimate an extrapolated sensitivity of 90%, based on the range of CSF genome counts found in Laos. Dried CSF filter paper spots could potentially help us to better understand the epidemiology of bacterial meningitis in resource-poor settings and guide empirical treatments and vaccination policies. PMID:23738720

Elliott, I; Dittrich, S; Paris, D; Sengduanphachanh, A; Phoumin, P; Newton, P N



Cerebrospinal fluid pressure1  

Microsoft Academic Search

The cerebrospinal fluid pressure at the foramen of Monro in man in the recumbent position is less than 100 mm water relative to atmospheric pressure. The oscillations in the pressure wave due to respiration and cardiac pulsation vary with the actual pressure and increase as the overall pressure rises. In man lying horizontally the oscillation at the foramen of Monro

K. C. Bradley



Low cerebrospinal fluid pressure headache  

Microsoft Academic Search

Opinion statement  \\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Alterations in cerebrospinal fluid (CSF) pressure lead to neurologic symptoms, the most common clinical manifestation of which\\u000a is headache. Typically, the headache is orthostatic and related to traction on pain-sensitive intracranial and meningeal structures,\\u000a distention on periventricular pain-sensitive areas, and direct pressure on pain conveying cranial nerves.\\u000a \\u000a \\u000a \\u000a \\u000a – \\u000a \\u000a Low CSF headache is a distinct and familiar syndrome

Christine M. Lay



Cerebrospinal Fluid Shunts  

Microsoft Academic Search

Hydrocephalus is a congenital or acquired condition in which cerebrospinal fluid (CSF) accumulates in the ventricles and the\\u000a subarachnoid space around the brain (Fig. 1). It can lead to an increase in intracranial pressure. It has existed since primitive\\u000a man roamed the earth. Man’s understanding of anatomy and physiology has often consisted mainly of myth and superstition. The\\u000a earliest recording

Edward Rustamzadeh; Cornelius H. Lam


Paucity of Initial Cerebrospinal Fluid Inflammation in Cryptococcal Meningitis is associated with subsequent Immune Reconstitution Inflammatory Syndrome  

PubMed Central

Background Cryptococcal meningitis (CM)-related immune reconstitution inflammatory syndrome (IRIS) complicates antiretroviral therapy (ART) in 20–40% of ART-naïve persons with AIDS and prior CM. Pathogenesis is unknown. Methods We compared initial CSF cultures, inflammatory markers and cytokine profiles in ART-naïve AIDS patients who did or did not subsequently develop IRIS after starting ART. We also compared results obtained at IRIS events or CM-relapse. Results Of 85 subjects with CM, 33 (39%) developed CM-IRIS and 5 (6%) developed culture-positive CM-relapse. At CM diagnosis, subjects subsequently developing IRIS had less inflammation, with decreased CSF leukocytes, protein, interferon-gamma (IFN-g), interleukin (IL)-6, IL-8, and tumor necrosis factor-alpha (TNF-a) compared with subjects not developing IRIS (P<.05). Initial CSF WBCs ?25 cells/?L and protein ?50 mg/dL were associated with development of IRIS (OR=7.2, 95%CI: 2.7 to 18.7, P<.001). Compared to baseline levels, we identified CSF elevations of IFN-g, TNF-a, G-CSF, VEGF, and eotaxin (CCL11) (P<.05) at IRIS but minimal inflammatory changes in those with CM relapse. Conclusions Patients who subsequently develop CM-IRIS exhibit less initial CSF inflammation at the time of CM diagnosis compared to those who do not develop IRIS. The inflammatory CSF cytokine profiles observed at time of IRIS can distinguish IRIS from CM-relapse.

Boulware, David R.; Bonham, Shulamith C.; Meya, David B.; Wiesner, Darin L.; Park, Gregory S.; Kambugu, Andrew; Janoff, Edward N.; Bohjanen, Paul R



Cerebrospinal fluid culture  


... infection is contagious, unless it is meningococcal meningitis. See also: Aseptic meningitis Cryptococcosis ... A laboratory culture poses no risk to you. For risks from the procedure done to get a CSF sample, see spinal tap .


Low Cerebrospinal Fluid Pressure Headache.  


Alterations in cerebrospinal fluid (CSF) pressure lead to neurologic symptoms, the most common clinical manifestation of which is headache. Typically, the headache is orthostatic and related to traction on pain-sensitive intracranial and meningeal structures, distention on periventricular pain-sensitive areas, and direct pressure on pain conveying cranial nerves. Low CSF headache is a distinct and familiar syndrome that is seen most frequently following lumbar puncture. In this clinical scenario, the diagnosis and proposed plan of treatment are obvious. Over the past decade, however, an emerging syndrome of spontaneous intracranial hypotension (SIH) is being recognized with increasing frequency. Most of these patients are found to have spontaneous CSF leaks and have unique, clinically distinct imaging findings, which confirm the diagnosis leading to appropriate treatment. Spontaneous intracranial hypotension is a relatively benign and usually self-limiting syndrome of orthostatic headache in association with one or more of numerous symptoms including nausea, vomiting, horizontal diplopia, unsteadiness or vertigo, altered hearing, neck pain/stiffness, interscapular pain, and occasionally visual field cuts. The headache itself, while often orthostatic, may initially be non-positional, may lose its orthostatic features, or rarely or never be orthostatic. It may be gradual, subacute, or thunderclap in onset. There may be a history of minor, antecedent trauma. By very definition, the opening CSF pressure is low, below 60 mm H(2)O, and often a "dry" tap is encountered. However, the pressure may be normal, especially with intermittent leaks and may vary tap to tap. Fluid analysis is normal. Brain (and occasionally spinal) MRI studies, with gadolinium enhancement should be undertaken. In patients with SIH, studies typically reveal diffuse pachymeningeal enhancement, frequently in association with "sagging"of the brain, tonsilar descent, and posterior fossa crowding. Spinal MRI is an up and coming investigational technique, which may be helpful even in the case of a normal brain MRI. Computed tomography myelography is the diagnostic study of choice and may follow radiocisternography, which often shows absence of activity over the convexities and early appearance of activity in the renal/urinary tract. Although conservative measures are often undertaken first, epidural blood patch (EBP) is the treatment of choice. For those who fail EBP, surgery may need to be undertaken in those cases with clearly identified leaks. PMID:12162924

Lay, Christine M.



Development of a Nested PCR for Detection of Cryptococcus neoformans in Cerebrospinal Fluid  

Microsoft Academic Search

We report the development of a nested-PCR-based assay for the detection of Cryptococcus neoformans in cerebrospinal fluid. The specificity and sensitivity of the test were assessed. The technique was then applied to 40 cerebrospinal fluid samples. We obtained positive reactions for all 21 clinical samples from patients who had been previously diagnosed as having cryptococcal meningitis by conventional techniques and




Macrophage migration inhibitory factor in cerebrospinal fluid from patients with central nervous system infection  

Microsoft Academic Search

INTRODUCTION: Macrophage migration inhibitory factor (MIF) plays an essential pathophysiological role in septic shock, but its role in central nervous system infection (CNS) remains to be defined. METHODS: We investigated cerebrospinal fluid (CSF) levels of MIF in 171 patients who were clinically suspected of having meningitis on admission. Of these, 31 were found to have purulent meningitis of known aetiology,

Christian Østergaard; Thomas Benfield



Evaluation of Tumor Marker S-100 in Cerebrospinal Fluid from Subjects with Nonischemic Brain Pathologies  

Microsoft Academic Search

In order to evaluate the S-100 concentration in cerebrospinal fluid from subjects with nonischemic brain damage, a total of 33 samples were analyzed: 11 from subjects in whom no organic disease could be found; 14 from patients with a diagnosis of lymphocytic or bacterial-fungal meningitis, and 8 from patients with acute lymphatic leukemia but no demonstrable signs of meningeal involvement.

Jose R. Infante; Miguel Torres-Avisbal; Antonio Martinez; Juan A. Vallejo; Cristobal Aguilera; Pablo Contreras; Ana Benitez; Jose M. Latre



Aetiological agents of cerebrospinal meningitis: a retrospective study from a teaching hospital in Ghana  

PubMed Central

Abstracts Background Meningitis is an important cause of morbidity and mortality in low-resource settings. In sub-Saharan Africa, the meningitis belt has been characterized by particularly high and seasonal incidences of bacterial meningitis extending throughout life. Despite the progress being made in treating the condition, the mortality rates continue to be high, ranging between 2% and 30% globally. In Ghana, the mortality rate of meningitis has been estimated to range from 36% to 50%. However little information is available on the pathogens contributing to meningitis and their antimicrobial susceptibilities. Updated information is essential to adjust the recommendations for empirical treatment or prevention of meningitis which could have immense implications for local and global health. Methods We retrospectively reviewed laboratory records of all patients suspected of bacterial meningitis who underwent a lumbar puncture from January 1, 2008 to December 31, 2010. Data were retrieved from laboratory record books and double entered into a Microsoft® excel spreadsheet. Results Records of 4,955 cerebrospinal fluid samples were analysed. Of these, 163 (3.3%, 95%CI: 2.8% to 3.8%) were confirmed meningitis and 106 (2.1%, 95%CI: 1.7% to 2.6%) were probable meningitis cases. Confirmed meningitis cases were made up of 117 (71.8%) culture positive bacteria, 19 (11.7%) culture positive Cryptococcus neoformans and 27(16.6%) Gram positive bacteria with negative culture. The most prevalent bacteria was Streptococcus pneumoniae 91 (77.7%), followed by E.coli 4 (3.4%), Salmonella species 4 (3.4%), Neisseria meningitidis 3 (2.5%), Pseudomonas species 3(2.5%) and others. Pneumococcal isolates susceptibility to penicillin, chloramphenicol and ceftriaxone were 98.9% (95%CI: 94.0% to 100.0%), 83.0% (95%CI: 73.4% to 90.1%) and 100.0% (95%CI: 95.8% to 100.0%) respectively. Conclusion Streptococcus pneumoniae is an important cause of meningitis among all age groups and its susceptibility to penicillin and ceftriaxone still remains very high. Ghanaians of all ages and possibly other developing countries in the meningitis belt could benefit from the use of the pneumococcal vaccine. Other bacterial and fungal pathogens should also be considered in the management of patients presenting with meningitis.



Accuracy of the cerebrospinal fluid results to differentiate bacterial from non bacterial meningitis, in case of negative gram-stained smear  

Microsoft Academic Search

ObjectiveThe aim of this study was to evaluate the usefulness of various laboratory results for differential diagnosis of bacterial (BM) and nonbacterial meningitis (NBM) with negative initial Gram stain.

Patrick Ray; Ghislaine Badarou-Acossi; Alain Viallon; David Boutoille; Martine Arthaud; David Trystram; Bruno Riou



Chemokine Levels and Chemokine Receptor Expression in the Blood and the Cerebrospinal Fluid of HIV-Infected Patients With Cryptococcal Meningitis and Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome.  


Background.?Human immunodeficiency virus-infected patients with treated cryptococcal meningitis who start combination antiretroviral therapy (cART) are at risk of further neurological deterioration, in part caused by paradoxical cryptococcosis-associated immune reconstitution inflammatory syndrome (C-IRIS). We hypothesized that C-IRIS is associated with alterations of chemokine receptor expression on T cells and chemokine concentrations in cerebrospinal fluid (CSF) that enhance recruitment of T-helper 1 cells and/or myeloid cells to the central nervous system. Methods.?In a prospective study of 128 human immunodeficiency virus-infected patients with cryptococcal meningitis who received antifungal therapy followed by cART, we examined the proportions of CD4(+) and CD8(+) T cells expressing CCR5 and/or CXCR3, in CSF and whole blood and the concentrations of CXCL10, CCL2, and CCL3 in stored CSF and plasma. Results.?The proportion of CD4(+) and CD8(+) T cells expressing CXCR3(+)CCR5(+) and the concentrations of CXCL10, CCL2 and CCL3 were increased in CSF compared with blood at cART initiation (P < .0001). Patients with C-IRIS (n = 26), compared with those with no neurological deterioration (n = 63), had higher CSF ratios of CCL2/CXCL10 and CCL3/CXCL10 and higher proportions of CXCR3(+)CCR5(+)CD8(+)T cells in CSF compared with blood at cART initiation (P = .03, .0053, and .02, respectively). Conclusion.?CD8(+) T-cell and myeloid cell trafficking to the central nervous system may predispose patients to C-IRIS. PMID:23908492

Chang, Christina C; Omarjee, Saleha; Lim, Andrew; Spelman, Tim; Gosnell, Bernadett I; Carr, William H; Elliott, Julian H; Moosa, Mohamed-Yunus S; Ndung'u, Thumbi; French, Martyn A; Lewin, Sharon R



Detection of transforming growth factor beta1 mRNA in cerebrospinal fluid cells of patients with meningitis by non-radioactive in situ hybridization  

Microsoft Academic Search

Meningitis is a serious disease mostly caused by viral or bacterial infections. In complicated cases it may lead to brain damage and death. The infection and cell damage result in a cellular and immunological response. Following this, a high secretion of cytokines can be expected. Cytokines, especially tumour necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1), promote the inflammatory reactions in

Ludgera M. Ossege; Bruno Voss; Thorsten Wiethege; Eckhart Sindern; Jean-Pierre Malin



Evaluation of adenosine deaminase activity and antibody to Mycobacterium tuberculosis antigen 5 in cerebrospinal fluid and the radioactive bromide partition test for the early diagnosis of tuberculosis meningitis  

Microsoft Academic Search

A number of different biochemical and serological tests have been described recently for the early and accurate diagnosis of tuberculous meningitis. None of these tests has yet gained widespread acceptance in clinical medicine or in microbiology laboratories. To investigate this problem we evaluated adenosine deaminase activity (ADA), an enzyme linked immunosorbent assay (ELISA) that detects antibody to antigen 5 of

Y M Coovadia; A Dawood; M E Ellis; H M Coovadia; T M Daniel



Microscopic examinations of human cerebrospinal fluid (CSF)  

NASA Astrophysics Data System (ADS)

The increase in inception rate connected with the cerebrospinal fluid have been observed recently. In the cerebrospinal fluid there are various types of suspension. There are cells and proteins which form different dispersion systems of given the sizes and concentrations among them. Finding out the physical processes occurring in the human cerebrospinal fluid is a problem of high importance. Coagulation, coalescence, aggregation and other physical processes in the cerebrospinal fluid depend on the state of health of the person who the sample was taken from. Thus it influences the concentration of suspension, its type and the sizes of suspended particles as well. In the paper the authors present the results of examinations of suspension in non-coloured human cerebrospinal fluid and the preliminary analysis of concentration of suspension and the sizes of suspended particles. The results were obtained by microscoping.

Staro?, Waldemar; Herbowski, Leszek; Gurgul, Henryk



Clinical pharmacokinetics of antibacterials in cerebrospinal fluid.  


In the past 20 years, an increased discrepancy between new available antibacterials and the emergence of multidrug-resistant strains has been observed. This condition concerns physicians involved in the treatment of central nervous system (CNS) infections, for which clinical and microbiological success depends on the rapid achievement of bactericidal concentrations. In order to accomplish this aim, the choice of drugs is based on their disposition toward the cerebrospinal fluid (CSF), which is influenced by the physicochemical characteristics of antibacterials. A reduced distribution into CSF has been documented for beta-lactams, especially cephalosporins and carbapenems, on the basis of their hydrophilic nature. However, they represent a cornerstone of the majority of combined therapeutic schemes for their ability to achieve bactericidal concentrations, especially in the presence of inflamed meninges. The good tolerability of beta-lactams makes possible high daily dose intensities, which may be associated with increased probability of cure. Furthermore, the adoption of continuous infusion seems to be a fruitful option. Fluoroquinolones, namely moxifloxacin, and antituberculosis drugs, together with the agents such as linezolid, reach the highest CSF/plasma concentration ratio, which is greater than 0.8, and for most of these drugs it is near 1. For all drugs that are currently used for the treatment of CNS infections, the evaluation of pharmacokinetic/pharmacodynamic parameters, on the basis of dosing regimens and their time-dependent or concentration-dependent pattern of bacterial killing, remains an important aspect of clinical investigation and medical practice. PMID:23605634

Di Paolo, Antonello; Gori, Giovanni; Tascini, Carlo; Danesi, Romano; Del Tacca, Mario



An Investigation of Cerebrospinal Fluid Shunt Valves.  

National Technical Information Service (NTIS)

The report represents the results of phase II of an investigation involving the development and evaluation of tests which can be used to demonstrate that a given Cerebrospinal Fluid (CSF) Shunt Valve will perform its intended regulating function. Included...

H. D. Keith X. Avula C. Schelich C. Watts



[Cerebrospinal fluid serotonin concentration in pyogenic and tick-borne encephalomeningitis].  


Cerebrospinal fluid (CSF) serotonin was determined in 38 patients with pyogenic meningitis and tick-borne encephalitis (TBE) before and after treatment. Increase of CSF serotonin concentration was observed in acute phase of pyogenic meningits and normalized after treatment. PMID:10463248

Siwak, E B; Pawlak, D; Buczko, W; Kondrusik, M; Hermanowska-Szpakowicz, T


Study of bacterial air pollution in an arid region of Africa affected by cerebrospinal meningitis  

PubMed Central

In 1968 and 1969, a study of the prevalence of airborne bacteria in different types of dwelling was carried out in Upper Volta and in Mali in order to determine the relationship between bacterial pollution of the air and the spread of cerebrospinal meningitis. In homes and schools in Upper Volta the total number of airborne bacteria, including those of oral origin, was found to be much higher during the dry season, when epidemics of cerebrospinal meningitis occur, than in the rainy periods. The study in Mali was carried out during an epidemic of cerebrospinal meningitis; two districts of the city of Bamako were chosen, those with the highest and lowest rates of infection. The number of airborne bacteria in the district of high incidence was found to be 10 times that in the district of low incidence. The study has shown that high counts of airborne bacteria and organisms of buccal origin are indicative of conditions that favour the spread of cerebrospinal meningitis. Sanitary measures to reduce the number of airborne bacteria would therefore be a useful means of combating epidemics of cerebrospinal meningitis in Africa.

Ghipponi, P.; Darrigol, J.; Skalova, R.; Cvjetanovic, B.



Pharmacokinetics and Cerebrospinal Fluid Concentration of Nafcillin in Pediatric Patients Undergoing Cerebrospinal Fluid Shunt Placement  

Microsoft Academic Search

Postoperative infection is among the most common complications in patients with cerebrospinal fluid shunt placement. Nafcillin is often used for prophylaxis but no pharmacokinetic data are available perioperatively in pediatric patients. The objectives of this study were to characterize the pharmacokinetics and determine the cerebrospinal concentrations of nafcillin. Ten patients (mean age 8.0 ± 5.6 years) received three doses of

Milap C. Nahata; Patty Fan-Havard; Edward J. Kosnik; Henry Bartkowski; William J. Barson



Paradoxical Postural Headaches in Cerebrospinal Fluid Leaks  

Microsoft Academic Search

Two patients with cerebrospinal fluid (CSF) leak, one at the level of fourth thoracic spine and another with undetermined level of leak, presented with paradoxical postural headaches in that the headaches were present when in a horizontal position and resolved if the patients were upright. One patient improved spontaneously and the other responded to a targeted epidural blood patch. Paradoxical

B Mokri; A J Aksamit; J LD Atkinson



Neuroactive steroids in periphery and cerebrospinal fluid  

Microsoft Academic Search

Some peripheral steroids penetrate the blood-brain barrier (BBB), providing at least substances for the CNS steroid metabolome. That is why the predictive value of the peripheral steroids appears to be comparable with that of the cerebrospinal fluid (CSF) steroids. The concentrations of the CSF steroids are pronouncedly lower in comparison with the ones in circulation. The available data indicate that

R. Kancheva; M. Hill; Z. Novák; J. Chrastina; L. Kancheva; L. Stárka



Human neuroglobin protein in cerebrospinal fluid  

Microsoft Academic Search

BACKGROUND: Neuroglobin is a hexacoordinated member of the globin family of proteins. It is predominantly localized to various brain regions and retina where it may play a role in protection against ischemia and nitric oxide-induced neural injury. Cerebrospinal fluid was collected from 12 chronic regional or systemic pain and 5 control subjects. Proteins were precipitated by addition of 50% 0.2

Begona Casado; Lewis K Pannell; Gail Whalen; Daniel J Clauw; James N Baraniuk



Cerebrospinal Fluid Shunt Infection by Neisseria sicca  

Microsoft Academic Search

Neisseria sicca is considered to be a nonpathogenic oral saprophyte. Presented here is an unusual case of cerebrospinal fluid (CSF) shunt infection by N. sicca. Although medical management of the common community-acquired meningitides, including infection by Neisseria meningitidis, is often successful in patients with CSF shunts, removal and replacement of the infected shunt was necessary in this case.

Galina Hornyik



Tegmental Defects and Cerebrospinal Fluid Otorrhea  

Microsoft Academic Search

Congenital tegmental defects that present as unsuspected cerebrospinal fluid (CSF) otorrhea are diagnostic and therapeutic challenges. We reviewed 5 such patients to determine an optimal strategy for evaluation. Five patients presented with watery otorrhea, 4 of them after ventilation tube placement, and only 1 with rhinorrhea. The preoperative analysis of middle ear effusion for ?2-transferrin was positive in 2\\/4, equivocal

Hannu J. Valtonen; Carl A. Geyer; Edward C. Tarlov; Carl B. Heilman; Dennis S. Poe



Cerebrospinal fluid may mediate CNS ischemic injury  

Microsoft Academic Search

BACKGROUND: The central nervous system (CNS) is extremely vulnerable to ischemic injury. The details underlying this susceptibility are not completely understood. Since the CNS is surrounded by cerebrospinal fluid (CSF) that contains a low concentration of plasma protein, we examined the effect of changing the CSF in the evolution of CNS injury during ischemic insult. METHODS: Lumbar spinal cord ischemia

Yanming F Wang; Judith K Gwathmey; Guorong Zhang; Sulpicio G Soriano; Shunli He; Yanguang Wang



The Treatment of Cerebrospinal Fluid Shunt Infections  

Microsoft Academic Search

It is our impression that the management strategy for infected cerebrospinal fluid (CSF) shunts varies significantly among pediatric neurosurgeons. The purpose of this paper is to present the results of a practice survey on the treatment of shunt infections which was distributed to all active members of the American Society of Pediatric Neurosurgeons (ASPN). Eighty-four of 129 ASPN members (65%)

William E. Whitehead; John R. W. Kestle



FDA Drug Safety Communication: Aseptic meningitis ...  

Center for Drug Evaluation (CDER)

... Meningitis is an inflammation of the protective membranes (the meninges ... In addition, cerebrospinal fluid white blood cell count differentials showed ... More results from


Comparative In Vitro Killing Activities of Meropenem, Imipenem, Ceftriaxone, and Ceftriaxone plus Vancomycin at Clinically Achievable Cerebrospinal Fluid Concentrations against Penicillin-Resistant Streptococcus pneumoniae Isolates from Children with Meningitis  

PubMed Central

The activities of meropenem, imipenem, ceftriaxone, and vancomycin were evaluated against 80 penicillin-susceptible and -resistant Streptococcus pneumoniae strains. Meropenem, imipenem, ceftriaxone, and vancomycin MICs at which 90% of the isolates are inhibited were 0.5, 0.25, 1, and 0.25 ?g/ml, respectively. Against penicillin-resistant strains, the best killing activity at cerebrospinal fluid concentrations was obtained with imipenem and ceftriaxone-vancomycin. However, while the killing activity of imipenem was significantly greater than that of meropenem, no significant difference was observed between the activities of meropenem and ceftriaxone-vancomycin.

Fitoussi, Frederic; Doit, Catherine; Benali, Karim; Bonacorsi, Stephane; Geslin, Pierre; Bingen, Edouard



Cerebrospinal fluid proteome of patients with acute Lyme disease  

PubMed Central

During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS) leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing a deep view into the proteome for patients diagnosed with early-disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma.

Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.; Warren, H. Shaw



Meningothelial cells participate in immunological processes in the cerebrospinal fluid.  


Meningothelial cells (MECs) form the innermost layer of the meningeal sheath and as such are in direct contact with the cerebrospinal fluid (CSF) likely influencing CSF composition. The CSF space is a site of active immunological processes. To investigate an immunological role of MECs, cytokine and chemokine secretion, phagocytotic and pinocytotic activity by MECs was analyzed following stimulation with lipopolysaccharide, phorbol ester or rotenone. Secretion of IL-6 and IL-8 by MECs increased in a dose dependent manner after stimulation concomitant with NF-?B activation. In addition, phagocytotic clearance by MECs was enhanced suggesting an immunological role for MECs in the CSF compartment and pointing to a possible connection to neurodegenerative processes. PMID:22261544

Fan, Bin; Bordigari, Giovanna; Flammer, Josef; Killer, Hanspeter E; Meyer, Peter; Neutzner, Albert



DNA single cell cytometry in lymphocytic pleocytosis of the cerebrospinal fluid  

Microsoft Academic Search

The value of DNA single-cell cytometry for the detection of neoplasia in Feulgen-stained cerebrospinal fluid cytological specimens was tested on 34 cases of Non-Hodgkin's lymphoma or leukemia and on 66 cases of viral or bacterial meningitis as a disease control group. The DNA content of 200 randomly chosen nuclei was measured on one pre-existing, cytologically representative slide per case, using

Stefan Biesterfeld; Bettina Bernhard; Stephan Bamborschke; Alfred Böcking



Weather conditions and cerebrospinal meningitis in Benin (Gulf of Guinea, West Africa).  


Over a 28-year period cerebrospinal meningitis, in sporadic as well as epidemic situations, mainly affected the Beninese territory from November to March, April or sometimes May. On the average, the acme occurred in February-March. A regression analysis confirmed that 14 to 34.5% of the temporal variability of the disease was due to the northern trade wind (harmattan) and a low absolute humidity in the northern areas, which constitute the main epidemiological pole of the country. On the contrary, cerebrospinal meningitis and climate turned out to be fully independent one from the other in the southernmost areas, where the harmattan is seldom experienced although the meningitis belt is at the present time spreading southwards. But the case-fatality ratio was especially high in the coastal region and during the off season, i.e. when endemic meningitis predominantly affected small children aged under one year. In any way, the climate-meningitis relationship proved to be weaker than is sometimes assumed, perhaps because this relationship is partly overshadowed by both anthropic effects (vaccination campaigns) and latency before disease outbreak. PMID:9384271

Besancenot, J P; Boko, M; Oke, P C



Cerebrospinal fluid secretion by the choroid plexus.  


The choroid plexus epithelium is a cuboidal cell monolayer, which produces the majority of the cerebrospinal fluid. The concerted action of a variety of integral membrane proteins mediates the transepithelial movement of solutes and water across the epithelium. Secretion by the choroid plexus is characterized by an extremely high rate and by the unusual cellular polarization of well-known epithelial transport proteins. This review focuses on the specific ion and water transport by the choroid plexus cells, and then attempts to integrate the action of specific transport proteins to formulate a model of cerebrospinal fluid secretion. Significant emphasis is placed on the concept of isotonic fluid transport across epithelia, as there is still surprisingly little consensus on the basic biophysics of this phenomenon. The role of the choroid plexus in the regulation of fluid and electrolyte balance in the central nervous system is discussed, and choroid plexus dysfunctions are described in a very diverse set of clinical conditions such as aging, Alzheimer's disease, brain edema, neoplasms, and hydrocephalus. Although the choroid plexus may only have an indirect influence on the pathogenesis of these conditions, the ability to modify epithelial function may be an important component of future therapies. PMID:24137023

Damkier, Helle H; Brown, Peter D; Praetorius, Jeppe



Spontaneous cerebrospinal fluid leak syndrome: report of 18 cases  

Microsoft Academic Search

We examined a group of 18 consecutive patients with spontaneous cerebrospinal fluid leak syndrome (SCSFLS) and investigated clinical, MRI, radioisotope findings and therapeutic outcome of this syndrome.

E. Ferrante; R. Wetzl; A. Savino; A. Citterio; A. Protti



Weather conditions and cerebrospinal meningitis in Benin (gulf of Guinea, West Africa)  

Microsoft Academic Search

Over a 28-year period cerebrospinal meningitis, in sporadic as well as epidemic situations, mainly affected the Beninese territory from November to March, April or sometimes May. On the average, the acme occured in February–March. A regression analysis confirmed that 14 to 34.5% of the temporal variability of the disease was due to the northern trade wind (harmattan) and a low

J. P. Besancenot; M. Boko; P. C. Oke




PubMed Central

We hypothesize that stasis of the cerebrospinal fluid (CSF) occurs commonly and is detrimental to health. Physiologic factors affecting the normal circulation of CSF include cardiovascular, respiratory, and vasomotor influences. The CSF maintains the electrolytic environment of the central nervous system (CNS), influences systemic acid-base balance, serves as a medium for the supply of nutrients to neuronal and glial cells, functions as a lymphatic system for the CNS by removing the waste products of cellular metabolism, and transports hormones, neurotransmitters, releasing factors, and other neuropeptides throughout the CNS. Physiologic impedance or cessation of CSF flow may occur commonly in the absence of degenerative changes or pathology and may compromise the normal physiologic functions of the CSF. CSF appears to be particularly prone to stasis within the spinal canal. CSF stasis may be associated with adverse mechanical cord tension, vertebral subluxation syndrome, reduced cranial rhythmic impulse, and restricted respiratory function. Increased sympathetic tone, facilitated spinal segments, dural tension, and decreased CSF flow have been described as closely related aspects of an overall pattern of structural and energetic dysfunction in the axial skeleton and CNS. Therapies directed at affecting CSF flow include osteopathic care (especially cranial manipulation), craniosacral therapy, chiropractic adjustment of the spine and cranium, Network Care (formerly Network Chiropractic), massage therapy (including lymphatic drainage techniques), yoga, therapeutic breathwork, and cerebrospinal fluid technique. Further investigation into the nature and causation of CSF stasis, its potential effects upon human health, and effective therapies for its correction is warranted.

Whedon, James M.; Glassey, Donald



Drug transport in brain via the cerebrospinal fluid  

PubMed Central

The human brain has no lymphatic system, but produces over a half-liter each day of cerebrospinal fluid. The cerebrospinal fluid is secreted at the choroid plexus and occupies the cavities of the four ventricles, as well as the cranial and spinal sub-arachnoid space. The cerebrospinal fluid moves over the surfaces of the brain and spinal cord and is rapidly absorbed into the general circulation. The choroid plexus forms the blood-cerebrospinal fluid barrier, and this barrier is functionally distinct from the brain microvascular endothelium, which forms the blood-brain barrier. Virtually all non-cellular substances in blood distribute into cerebrospinal fluid, and drug entry into cerebrospinal fluid is not an index of drug transport across the blood-brain barrier. Drug injected into the cerebrospinal fluid rapidly moves into the blood via bulk flow, but penetrates into brain tissue poorly owing to the limitations of diffusion. Drug transport into cerebrospinal fluid vs. brain interstitial fluid requires knowledge of the relative expression of transporters at the choroid plexus versus the brain microvascular endothelium.



Novel cyclovirus in human cerebrospinal fluid, Malawi, 2010-2011.  


To identify unknown human viruses, we analyzed serum and cerebrospinal fluid samples from patients with unexplained paraplegia from Malawi by using viral metagenomics. A novel cyclovirus species was identified and subsequently found in 15% and 10% of serum and cerebrospinal fluid samples, respectively. These data expand our knowledge of cyclovirus diversity and tropism. PMID:23968557

Smits, Saskia L; Zijlstra, Ed E; van Hellemond, Jaap J; Schapendonk, Claudia M E; Bodewes, Rogier; Schürch, Anita C; Haagmans, Bart L; Osterhaus, Albert D M E



A chronic fatigue syndrome – related proteome in human cerebrospinal fluid  

Microsoft Academic Search

BACKGROUND: Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. METHODS: Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50

James N. Baraniuk; Begona Casado; Hilda Maibach; Daniel J. Clauw; Lewis K. Pannell; Sonja Hess S



Proteomic analysis of multiple sclerosis cerebrospinal fluid.  


Two-dimensional gel electrophoresis and peptide mass fingerprinting were used to identify proteins in cerebrospinal fluid (CSF) pooled from three patients with multiple sclerosis (MS) and in CSF pooled from three patients with non-MS inflammatory central nervous system (CNS) disorders. Resolution of CSF proteins on three pH gradients (3-10, 4-7 and 6-11) enabled identification of a total of 430 spots in the MS CSF proteome that represented 61 distinct proteins. The gels containing MS CSF revealed 103 protein spots that were not seen on control gels. All but four of these 103 spots were proteins known to be present in normal human CSF. The four exceptions were: CRTAC-IB (cartilage acidic protein), tetranectin (a plasminogen-binding protein), SPARC-like protein (a calcium binding cell signalling glycoprotein), and autotaxin t (a phosphodiesterase). It remains unknown whether these four proteins are related to the cause and pathogenesis of MS. PMID:15222687

Hammack, B N; Fung, K Y C; Hunsucker, S W; Duncan, M W; Burgoon, M P; Owens, G P; Gilden, D H



Glycoproteomics of cerebrospinal fluid in neurodegenerative disease  

NASA Astrophysics Data System (ADS)

Cerebrospinal fluid (CSF) from individual patients with Alzheimer's disease (AD) was separated by narrow range two-dimensional (2D) gel electrophoresis and analyzed by electrospray FT-ICR MS in this glycoproteomic study. Because several altered proteins in the comparison between AD patients and healthy controls individuals are isoforms of glycoproteins, it is important to determine if the modifying glycans are also altered. FT-ICR MS and fragmentation of glycopeptides with infrared multiphoton dissociation (IRMPD) offers abundant fragment ions through breakage at the glycosidic linkages with excellent mass accuracy, which facilitates the structural determination of the site-specific N-linked glycosylation. We present results from a structural comparison of proteins from three AD patients and three control individuals of different glycosylated isomers of [alpha]-1-antitrypsin, [beta]-trace and apolipoprotein J.

Sihlbom, Carina; Davidsson, Pia; Emmett, Mark R.; Marshall, Alan G.; Nilsson, Carol L.



Cerebrospinal fluid leak secondary to chiropractic manipulation  

PubMed Central

Background: There is a paucity of quality data on the incidence of adverse outcomes of chiropractic manipulation. Spontaneous intracranial hypotension (SIH) subsequent to cervical spinal manipulation has been documented. However, no imaging correlates have previously been presented demonstrating a clear causal relationship to manipulation with follow-up and correlating with clinical symptomatology. Case Description: We present a case of subacute cervical cerebrospinal fluid (CSF) leak resulting from chiropractic manipulation of the cervical spine. The patient is a 29-year-old female who received manipulation one week prior to developing symptoms of severe orthostatic headache, nausea, and vomiting. Magnetic resonance imaging (MRI) revealed a new C5-C6 ventral CSF collection. Symptomatic onset corresponded with the recent cervical chiropractic adjustment. We present serial imaging correlating with her symptomatology and review the pertinent literature on complications of chiropractic manipulation. Conclusion: Our case of ventral CSF leak with symptoms of intracranial hypotension demonstrated spontaneous symptomatic resolution without permanent neurological sequelae.

Kusnezov, Nicholas A.; Velani, Shamsha A.; Lu, Daniel C.



Cerebrospinal fluid leakage--reliable diagnostic methods.  


Prompt diagnosis and early treatment of cerebrospinal fluid (CSF) leakage minimizes the risk of severe complications. In patients presenting with clear fluid nasal discharge it is important to identify the nature of the rhinorrhea. The CSF leakage may occur as post-traumatic, iatrogenic, spontaneous or idiopathic rhinorrhea. The differential diagnosis of CSF rhinorrhea often presents a challenging problem. The confirmation of CSF rhinorrhea and localization of the leakage may be diagnosed by CT, MRI cisternography and MRI cisternography in combination with single photon emission tomography or radioisotopic imaging. Although these methods allow estimation of the CSF leakage with high accuracy, they are expensive and invasive procedures. Therefore, biochemical methods are still used in the differentiation. Although the most common diagnostic method for screening CSF leakage is glucose oxidase, its diagnostic sensitivity and specificity is generally unsatisfactory. False negative results may occur with bacterial contamination and false positive results are common in diabetic patients. Glucose detection is not recommended as a confirmatory test. As such, other biomarkers of the CSF leakage, such as beta-2-transferrin (beta-2 trf) and beta-trace protein (betaTP) are necessary to identify and confirm of this condition. PMID:21334321

Mantur, Maria; ?ukaszewicz-Zaj?c, Marta; Mroczko, Barbara; Ku?akowska, Alina; Ganslandt, Oliver; Kemona, Halina; Szmitkowski, Maciej; Drozdowski, Wies?aw; Zimmermann, Rüdiger; Kornhuber, Johannes; Lewczuk, Piotr



Proteome analysis of chick embryonic cerebrospinal fluid.  


During early stages of embryo development, the brain cavity is filled with embryonic cerebrospinal fluid (E-CSF), a complex fluid containing different protein fractions that contributes to the regulation of the survival, proliferation and neurogenesis of the neuroectodermal stem cells. Using 2-DE, protein sequencing and database searches, we identified and analyzed the proteome of the E-CSF from chick embryos (Gallus gallus). We identified 26 different gene products, including proteins related to the extracellular matrix, proteins associated with the regulation of osmotic pressure and metal transport, proteins related to cell survival, MAP kinase activators, proteins involved in the transport of retinol and vitamin D, antioxidant and antimicrobial proteins, intracellular proteins and some unknown proteins. Most of these gene products are involved in the regulation of developmental processes during embryogenesis in systems other than E-CSF. Interestingly, 14 of them are also present in adult human CSF proteome, and it has been reported that they are altered in the CSF of patients suffering neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis is a key contribution to the general understanding of CNS development, and may also contribute to greater knowledge of these human diseases. PMID:16287170

Parada, Carolina; Gato, Angel; Aparicio, Mariano; Bueno, David



Cerebrospinal fluid pulse pressure waveform analysis in hydrocephalic children  

Microsoft Academic Search

Analysis of cerebrospinal fluid pulse pressure was reported to be useful in the assessment of the cerebrospinal pressure-volume compensation. The method for the estimation of high-frequency centroid (HFC) was modified and used to verify the correlation between HFC and other compensatory parameters investigated by means of the lumbar infusion test in 94 hydrocephalic children. The results confirm that in hydrocephalus

W. Zabolotny; M. Czosnyka; A. Walencik



Radioimmunological Evidence for Beta-Endorphin in Human Cerebrospinal Fluid.  

National Technical Information Service (NTIS)

Beta-endorphin-like immunoreactivity in human cerebrospinal fluid was determined by two different radioimmunoassays. Measurements made using a bought RIA-kit (Immuno Nuclear Corporation) produced results which were too high compared to results from the li...

M. Graf



Observations on an Epidemic of Cerebrospinal Meningitis in Cyprus and the Record of a Prophylactic Experiment  

PubMed Central

After a lapse of twenty-five years cerebrospinal meningitis appeared again in epidemic from during 1936-37. A prophylactic inoculation experiment was undertaken during the autumn of 1937, a few months before the second epidemic season was due to begin. Season 1936-37—836 cases—284 deaths. Season 1937-38 (after inoculation)—298 cases—81 deaths. Season 1938-39—122 cases—51 deaths (to end of May, 1939). During the second season conditions were suitable for the continuance of the epidemic. We do not think that we obtained a false result by inoculating on a waning epidemic. Our results are inconclusive because owing to the sharp decline in the morbidity neither control nor inoculated groups were fully at risk. But our results are good enough to recommend a further trial of prophylaxis in future epidemics. The percentage of the population inoculated is an important factor. The aim should be 100%. The experiment should aim at controlling not only the meningococcal carrier rate but also the general catarrh rate. We suggest that the rapid passage of the meningoccocus in association with an epidemic of nasopharyngeal catarrh raises the virulence of the meningococcus. As the opportunity of a second experience in the prevention of cerebrospinal meningitis by prophylactic inoculation seldom occurs to an individual, we take this chance of making recommendations for guiding future experiments.

Maclean, I. H.; Bevan, C. E.




Microsoft Academic Search

Glucose levels in 154 random specimens of lumbar cerebrospinal fluid, normal as regards cell and protein content, were estimated by the glucose-oxidase method and a mean value of 60.5 mg.\\/100 ml. (S.D. 7.3) was obtained.In 33 fasting patients subject to air encephalography the mean cerebrospinal fluid (C.S.F.) glucose level was 56.5 mg., and mean blood glucose level 65.5 mg. with

Vincent Marks



Cerebrospinal Fluid Space Alterations in Melancholic Depression  

PubMed Central

Melancholic depression is a biologically homogeneous clinical entity in which structural brain alterations have been described. Interestingly, reports of structural alterations in melancholia include volume increases in Cerebro-Spinal Fluid (CSF) spaces. However, there are no previous reports of CSF volume alterations using automated whole-brain voxel-wise approaches, as tissue classification algorithms have been traditionally regarded as less reliable for CSF segmentation. Here we aimed to assess CSF volumetric alterations in melancholic depression and their clinical correlates by means of a novel segmentation algorithm (‘new segment’, as implemented in the software Statistical Parametric Mapping-SPM8), incorporating specific features that may improve CSF segmentation. A three-dimensional Magnetic Resonance Image (MRI) was obtained from seventy patients with melancholic depression and forty healthy control subjects. Although imaging data were pre-processed with the ‘new segment’ algorithm, in order to obtain a comparison with previous segmentation approaches, tissue segmentation was also performed with the ‘unified segmentation’ approach. Melancholic patients showed a CSF volume increase in the region of the left Sylvian fissure, and a CSF volume decrease in the subarachnoid spaces surrounding medial and lateral parietal cortices. Furthermore, CSF increases in the left Sylvian fissure were negatively correlated with the reduction percentage of depressive symptoms at discharge. None of these results were replicated with the ‘unified segmentation’ approach. By contrast, between-group differences in the left Sylvian fissure were replicated with a non-automated quantification of the CSF content of this region. Left Sylvian fissure alterations reported here are in agreement with previous findings from non-automated CSF assessments, and also with other reports of gray and white matter insular alterations in depressive samples using automated approaches. The reliable characterization of CSF alterations may help in the comprehensive characterization of brain structural abnormalities in psychiatric samples and in the development of etiopathogenic hypotheses relating to the disorders.

Via, Esther; Cardoner, Narcis; Pujol, Jesus; Martinez-Zalacain, Ignacio; Hernandez-Ribas, Rosa; Urretavizacaya, Mikel; Lopez-Sola, Marina; Deus, Joan; Menchon, Jose Manuel; Soriano-Mas, Carles



Enrichment of cerebrospinal fluid samples on cell culture for enhancement of sensitivity of mumps and enterovirus detection by multiplex RT-PCR  

Microsoft Academic Search

It has been demonstrated that the detection of enteroviruses and mumps virus nucleic acid in cerebrospinal fluid (CSF) specimens improves the management of the patients with aseptic meningitis. To determine the effect of overnight enrichment of mumps and enteroviruses in CSF samples on cell culture for increasing the sensitivity of viral detection, we developed a multiplex reverse transcriptase-polymerase chain reaction

Masoumeh Kermanian; Hoorieh Soleimanjahi; Ehsan Arefian; Taravat Bamdad



The bacterial meningitis score to distinguish bacterial from aseptic meningitis in children from sao paulo, Brazil.  


In a retrospective cohort of 494 children with meningitis in Sao Paulo, Brazil, the Bacterial Meningitis Score identified all the children with bacterial meningitis (sensitivity 100%, 95% confidence interval: 92-100% and negative predictive value 100%, 95% confidence interval: 98-100%). Addition of cerebrospinal fluid lactate to the score did not improve clinical prediction rule performance. PMID:24008742

Filho, Eduardo Mekitarian; Horita, Sérgio Massaru; Gilio, Alfredo Elias; Alves, Anna Cláudia Dominguez; Nigrovic, Lise E



Surgical Technique for the Prevention of Cerebrospinal Fluid Leakage After Bifrontal Craniotomy.  


BACKGROUND: Cerebrospinal fluid leakage and meningitis caused by frontal sinus (FS) exposure are characteristic complications of bifrontal craniotomy used for treating skull base tumors and anterior communicating artery aneurysms. Prevention of these complications is of utmost importance. We describe in detail our procedure for sealing exposed FSs during bifrontal craniotomy and present the results and outcomes of the procedure. METHODS: A total of 51 consecutive patients who had undergone bifrontal craniotomy for tuberculum sellae meningiomas, craniopharyngiomas, anterior cerebral artery aneurysms, or other frontal skull base lesions at our institute were selected for the study. Our technique for sealing exposed FSs is described below. The mucosa was sterilized using surgical cotton dipped in iodine. After craniotomy, the exposed mucosa was sealed using 7-0 nylon sutures, whereas Gelfoam with fibrin glue was used to ensure watertight closure. The exposed portions of the FSs were covered by bone covers made of internal table bone and sealed. As a final layer, frontal periosteal flaps were sutured to the frontal base dura mater. RESULTS: Postoperative cerebrospinal fluid leakage or meningitis did not occur in any of our patients. CONCLUSION: Our results indicate the effectiveness of our technique in the prevention of FS-related postoperative complications. PMID:23314023

Murai, Yasuo; Mizunari, Takayuki; Kobayashi, Shiro; Teramoto, Akira



New techniques and technology to repair cerebrospinal fluid rhinorrhea.  


Cerebrospinal fluid rhinorrhea occurs as a result of abnormal communication between the subarachnoid space and the pneumatized portion of the skull base, the paranasal sinuses and the middle ear. Conservative measures may be sufficient in the management of cerebrospinal fluid rhinorrhea, but, in some cases, surgical treatment may be required. Transnasal endoscopic techniques are constantly being used in preference to the intra- and extracranial approaches. Recently, image guidance systems have been adopted in neurosurgery, skull base and paranasal sinus surgery. The present report refers to 4 cases of nasal cerebrospinal fluid rhinorrhea leak successfully treated with a transnasal endoscopic approach using various techniques and materials to close the bone defect, in 2 of which, the navigation system (Stealth Station Treon ENT Image Guidance System with Landmark X, Software, Medtronic, XOMED, Jacksonville, FL, USA) was also used. In all cases, correct localization and repair of the leak was achieved and no major complications occurred. Following a review of the literature, the Authors conclude that, at present, transnasal endoscopic repair of cerebrospinal fluid rhinorrhea is the surgical treatment of choice when the techniques and materials are correctly used. Furthermore, preliminary findings indicate that it is possible to make routine use of the navigation systems and that this technology may be usefully employed, above all, in the management of cerebrospinal fluid leaks. PMID:15584583

Paludetti, G; Sergi, B; Rigante, M; Campioni, P; Galli, J



[Magnetic resonance in dural post-puncture headache in patient with cerebrospinal fluid hypotension].  


Magnetic resonance imaging (MRI) has allowed us to establish a set of radiologic signs associated with intracranial hypotension syndrome. Findings are partly influenced by cerebral displacement. Intracranial hypotension syndrome is characterized by a decrease in cerebrospinal fluid (CSF) pressure to less than 60 mm H2O associated with occipital headache radiating to the frontal and temporal zones. For diagnostic purposes, the most common cause is anesthetic or therapeutic dural puncture, although spontaneous CSF leakage can occur. CSF protein and lymphocyte counts may be high, while the cranial meninges biopsy is normal. MRI images may show a descended brain, taking the start of the sylvian aqueduct and the location of the cerebellar amygdalae as points of reference; diminished size of the subarachnoidal cisterns and occasionally of the cerebral ventricles; meningeal enhancement from increased uptake of the contrast solution; subdural hygromas and hematomas; and pituitary enlargement. Paraspinal fluid and dilated epidural veins may be observed. Radiologic images and clinical signs are related. When CSF pressure is very low, there is greater meningeal enhancement, subdural collection and cerebral displacement. Findings gradually disappear as symptoms diminish. The signs and symptoms that might develop during intracranial hypotension syndrome vary according to the brain structure that might be affected during descent, repositioning and the traction of anchoring structures. MRI allows the degree of cerebral and spinal involvement to be ascertained, to predict whether resolution of the clinical picture will be early or late and to visualize the effect of approaches to reducing CSF leakage. PMID:12025253

Reina, M A; Alvarez-Linera, J; López, A; Benito-León, J; De Andrés, J A; Sola, R G



Counterimmunoelectrophoresis in Diagnosis of Meningococcal Meningitis.  

National Technical Information Service (NTIS)

Cerebrospinal fluid (CSF) specimens from 357 purulent meningitis patients were examined by culture, gram stain, and counterimmunoelectrophoresis (CIE). The etiology was N. meningitidis in 259 patients, other bacteria in 16 patients, and could not be deter...

J. E. Sippel G. I. Higashi N. I. Girgis



Application of transport phenomena analysis technique to cerebrospinal fluid.  


The study of hydrocephalus and the modeling of cerebrospinal fluid flow have proceeded in the past using mathematical analysis that was very capable of prediction phenomenonologically but not well in physiologic parameters. In this paper, the basis of fluid dynamics at the physiologic state is explained using first established equations of transport phenomenon. Then, microscopic and molecular level techniques of modeling are described using porous media theory and chemical kinetic theory and then applied to cerebrospinal fluid (CSF) dynamics. Using techniques of transport analysis allows the field of cerebrospinal fluid dynamics to approach the level of sophistication of urine and blood transport. Concepts such as intracellular and intercellular pathways, compartmentalization, and tortuosity are associated with quantifiable parameters that are relevant to the anatomy and physiology of cerebrospinal fluid transport. The engineering field of transport phenomenon is rich and steeped in architectural, aeronautical, nautical, and more recently biological history. This paper summarizes and reviews the approaches that have been taken in the field of engineering and applies it to CSF flow. PMID:24091435

Lam, C H; Hansen, E A; Hall, W A; Hubel, A



New cephalosporins cefotaxime, cefpimizole, BMY 28142, and HR 810 in experimental pneumococcal meningitis in rabbits.  

PubMed Central

Four new cephalosporins, cefotaxime, cefpimizole (U 63196E), BMY 28142, and HR 810 were evaluated in experimental pneumococcal meningitis. Cefotaxime penetrated only moderately into the cerebrospinal fluid of rabbits with meningitis, whereas cefpimizole, BMY 28142, and HR 810 all exhibited unusually good penetration. The bactericidal activity in infected cerebrospinal fluid was comparable for the four drugs.

Tauber, M G; Hackbarth, C J; Scott, K G; Rusnak, M G; Sande, M A



Rapid and sensitive detection of enteroviruses in specimens from patients with aseptic meningitis.  

PubMed Central

A 5-h PCR assay (Amplicor enterovirus test) was compared with viral culture for the detection of enteroviruses in cerebrospinal fluid. Of the cerebrospinal fluid specimens collected during a summer outbreak of aseptic meningitis, 34% were positive by viral culture whereas 66% were positive by the Amplicor PCR, suggesting that this technique improves the diagnosis of enteroviral meningitis.

Yerly, S; Gervaix, A; Simonet, V; Caflisch, M; Perrin, L; Wunderli, W



Alterations in cerebrospinal fluid dopamine metabolites following physostigmine infusion  

Microsoft Academic Search

The effect of IV physostigmine administration on the cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) in normal subjects was determined. After an adjustment for differing CSF concentrations of probenecid, physostigmine was found to elevate CSF HVA and DOPAC concentrations. The authors discuss these changes in CSF HVA and DOPAC and their possible relationship to the

Kenneth L. Davis; Kym F. Faull; Leo E. Hollister; Jack D. Barchas; Philip A. Berger



The function and structure of the cerebrospinal fluid outflow system  

Microsoft Academic Search

This review traces the development of our understanding of the anatomy and physiological properties of the two systems responsible for the drainage of cerebrospinal fluid (CSF) into the systemic circulation. The roles of the cranial and spinal arachnoid villi (AV) and the lymphatic outflow systems are evaluated as to the dominance of one over the other in various species and

Michael Pollay



Quantification of Free Fatty Acids in Human Cerebrospinal Fluid  

Microsoft Academic Search

Free fatty acids (FFA) in cerebrospinal fluid (CSF) are well-recognized markers of brain damage in animal studies. Information is limited regarding human CSF in both normal and pathological conditions. Samples of CSF from 73 patients, who had undergone lumbar puncture for medically indicated reasons, came from a core laboratory upon completion of ordered tests. Using high performance liquid chromatography, mean

J. G. Pilitsis; F. G. Diaz; J. M. Wellwood; M. H. O'Regan; M. R. Fairfax; J. W. Phillis; W. M. Coplin



More Than the Brain's Drain: Does Cerebrospinal Fluid Help the Brain Convey Messages?  

ERIC Educational Resources Information Center

|Examines the role of cerebrospinal fluid (CSF), a clear, colorless liquid that constantly bathes the brain and spinal cord. Scientists argue that cerebrospinal fluid carries important signals for sleep, appetite, and sex. Evaluates past and current research documenting the purpose of cerebrospinal fluid in the brain. (CCM)|

Travis, John



C-reactive protein is useful in distinguishing Gram stain–negative bacterial meningitis from viral meningitis in children  

Microsoft Academic Search

Objective: To clarify to what extent Gram stain–negative bacterial meningitis can be distinguished from viral meningitis by assessment of cerebrospinal fluid (CSF) and blood indices and serum C-reactive protein (CRP) in children over 3 months of age. Design: Common CSF indices, blood leukocyte counts, and serum CRP values were compared between patients with bacterial meningitis who had a positive CSF

Päivi Sormunen; Markku J. T. Kallio; Terhi Kilpi; Heikki Peltola



Cysticercus Antigens in Cerebrospinal Fluid Samples from Patients with Neurocysticercosis  

Microsoft Academic Search

Antigens were detected in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti- Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A group of NC patients (n 174) were studied (NC), including 40 patients in different phases of the disease. ELISAs carried




Mollaret’s Meningitis  

Microsoft Academic Search

Pierre Mollaret is mainly known for his contributions to infectious diseases and their prevention. He also described benign, recurrent endothelio-leukocytic meningitis in three patients who had short-lived recurrent attacks of fever, headache and vomiting caused by sterile meningitis, with ‘fantomes cellulaires’ (cell ghosts) in the cerebrospinal fluid. Identical symptoms are caused by Herpes simplex virus-2 and other viruses. The term

J. M. S. Pearce



Measurement of Cerebrospinal Fluid Output through External Ventricular Drainage in One Hundred Infants and Children: Correlation with Cerebrospinal Fluid Production  

Microsoft Academic Search

Objective: Cerebrospinal fluid (CSF) production rates influence shunt design and the care of children with hydrocephalus. Measurement of hourly CSF output through external ventricular drainage (EVD) reflects the CSF production. In the present study, hourly CSF outputs in children with hydrocephalus were measured while they were treated with EVD and correlated with the age, sex and body weight of the

Takasumi Yasuda; Tadanori Tomita; David G. McLone; Mark Donovan



Cerebrospinal Fluid Cytokine Levels and Cognitive Impairment in Cerebral Malaria  

PubMed Central

Cerebrospinal fluid (CSF) and serum levels of 12 cytokines or chemokines important in central nervous system (CNS) infections were measured in 76 Ugandan children with cerebral malaria (CM) and 8 control children. As compared with control children, children with cerebral malaria had higher cerebrospinal fluid levels of interleukin (IL)-6, CXCL-8/IL-8, granulocyte-colony stimulating factor (G-CSF), tumor necrosis factor-? (TNF-?), and IL-1 receptor antagonist. There was no correlation between cerebrospinal and serum cytokine levels for any cytokine except G-CSF. Elevated cerebrospinal fluid but not serum TNF-? levels on admission were associated with an increased risk of neurologic deficits 3 months later (odds ratio 1.55, 95% CI: 1.10, 2.18, P = 0.01) and correlated negatively with age-adjusted scores for attention (Spearman rho, -0.34, P = 0.04) and working memory (Spearman rho, -0.32, P = 0.06) 6 months later. In children with cerebral malaria, central nervous system TNF-? production is associated with subsequent neurologic and cognitive morbidity.

John, Chandy C.; Panoskaltsis-Mortari, Angela; Opoka, Robert O.; Park, Gregory S.; Orchard, Paul J.; Jurek, Anne M.; Idro, Richard; Byarugaba, Justus; Boivin, Michael J.



Postoperative cerebrospinal fluid leak after septoplasty: A potential complication of occult anterior skull base encephalocele  

PubMed Central

Postoperative cerebrospinal fluid (CSF) rhinorrhea after septoplasty is a known entity resulting from errors in surgical technique and improper handling of the perpendicular plate of the ethmoid bone. When these occur, urgent management is necessary to prevent deleterious sequelae such as meningitis, intracranial abscess, and pneumocephalus. Encephaloceles are rare occurrences characterized by herniation of intracranial contents through a skull base defect that can predispose patients to CSF rhinorrhea. In this report, we present a case of CSF rhinorrhea occurring 2 weeks after septoplasty likely from manipulation of an occult anterior skull base encephalocele. To our knowledge, no previous similar case has been reported in the literature. Otolaryngologists should be aware of the possibility of occult encephaloceles while performing septoplasties because minimal manipulation of these entities may potentially result in postoperative CSF leakage.

Soni, Resha S.; Choudhry, Osamah J.; Liu, James K.



Cerebrospinal fluid obstruction and malabsorption in human neonatal hydrocephaly  

Microsoft Academic Search

Introduction  The pathophysiology involved in human neonatal high-pressure hydrocephalus (HC) includes both cerebrospinal fluid (CSF) malabsorption and obstruction.Objective  The aim was to estimate the relative contribution between CSF malabsorption and obstruction in three different etiological groups of neonatal high-pressure HC by assessment of specific CSF biomarkers indicative of growth factor- and fibrosis-related CSF malabsorption (transforming growth factor beta-1 (TGF beta-1), aminoterminal propeptide

Axel Heep; Peter Bartmann; Birgit Stoffel-Wagner; Arie Bos; Eelco Hoving; Oebele Brouwer; Albert Teelken; Carlo Schaller; Deborah Sival



The electrical conductivity of human cerebrospinal fluid at body temperature  

Microsoft Academic Search

The electrical conductivity of human cerebrospinal fluid (CSF) from seven patients was measured at both room temperature (25 C) and body temperature (37 C). Across the frequency range of 10Hz-10 kHz, room temperature conductivity was 1.45 S\\/m, but body temperature conductivity was 1.79 S\\/m, approximately 23% higher. Modelers of electrical sources in the human brain have underestimated human CSF conductivity

Stephen B. Baumann; David R. Wozny; Shawn K. Kelly; Frank M. Meno



Dynamics of brain-derived proteins in cerebrospinal fluid  

Microsoft Academic Search

Background: The recent theory of blood–cerebrospinal fluid (CSF) barrier function and dysfunction connects molecular flux and CSF flow rate. A reduced CSF flow rate is sufficient to account for the observed hyperbolic relation between different blood-derived protein concentrations in CSF in cases of a blood–CSF barrier dysfunction. Methods: The dynamics of brain-derived proteins in CSF are investigated with reference to

Hansotto Reiber



Effect of Cerebral Injury on Cerebrospinal Fluid Cyclic AMP Concentration  

Microsoft Academic Search

Cerebrospinal fluid (CSF) cyclic adenosine-3’,5’-monophosphate (cAMP) was measured in rabbits after experimental brain injury as well as in patients with cerebral contusion and cerebral concussion. In rabbits a marked elevation lasting for two weeks was observed. From the third week onwards after the injury the CSF cAMP concentration was lower than the basal level before the injury. Dexamethasone partly inhibited

V. V. Myllylä



Gelsolin in Cerebrospinal Fluid as a Potential Biomarker of Epilepsy  

Microsoft Academic Search

Gelsolin is an actin regulatory protein that generally distributed in a wide variety of body tissues, especially the brain\\u000a tissues and cerebrospinal fluid. In this study we found that lumbar CSF-gelsolin concentrations markedly decreased in epileptic\\u000a patients by enzyme linked immunosorbent assay. In order to help judge the result, we determined gelsolin expression in temporal\\u000a lobe tissues of patients with

Xi Peng; Xiaogang Zhang; Liang Wang; Qiong Zhu; Jing Luo; Wei Wang; Xuefeng Wang


Amyloid and tau cerebrospinal fluid biomarkers in HIV infection  

Microsoft Academic Search

BACKGROUND: Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. METHODS: In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPP? and sAPP?), amyloid beta fragment 1-42 (A?1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of

Magnus Gisslén; Jan Krut; Ulf Andreasson; Kaj Blennow; Paola Cinque; Bruce J Brew; Serena Spudich; Lars Hagberg; Lars Rosengren; Richard W Price; Henrik Zetterberg



Cerebrospinal fluid acetylcholinesterase and choline measurements in Huntington's disease  

Microsoft Academic Search

The caudate nucleus has the highest acetylcholinesterase (AChE) activity in the brain and it has been shown that autopsied brain tissue of patients with Huntington's disease (HD) have reduced levels of acetylcholine. Because of these findings, the cholinergic function in HD was studied by measuring cerebrospinal fluid (CSF) choline levels and AChE activity during a randomized, double-blind, cross-over, placebo-controlled clinical

B. V. Manyam; E. Giacobini; J. A. Colliver



Entry of diazepam and its major metabolite into cerebrospinal fluid  

Microsoft Academic Search

Five dogs received a single 1.0 mg\\/kg dose of diazepam (DZ) IV. Concentrations of DZ and its major metabolite desmethyldiazepam (DMDZ) were simultaneously measured in plasma and cisternal cerebrospinal fluid (CSF) for up to 8 h after the dose by electron-capture gas-liquid chromatography. DZ was rapidly eliminated from plasma (half-life 0.3–1.3 h); DZ disappearance was mirrored by formation of DMDZ,

David J. Greenblatt; Hermann R. Ochs; Brian L. Lloyd



Sleep deprivation increases oleoylethanolamide in human cerebrospinal fluid  

Microsoft Academic Search

This study investigated the role of two fatty acid ethanolamides, the endogenous cannabinoid anandamide and its structural\\u000a analog oleoylethanolamide in sleep deprivation of human volunteers. Serum and cerebrospinal fluid (CSF) samples were obtained\\u000a from 20 healthy volunteers before and after a night of sleep deprivation with an interval of about 12 months. We found increased\\u000a levels of oleoylethanolamide in CSF (P = 0.011)

Dagmar Koethe; Daniela Schreiber; Andrea Giuffrida; Christian Mauss; Johannes Faulhaber; Bernd Heydenreich; Martin Hellmich; Rudolf Graf; Joachim Klosterkötter; Daniele Piomelli; F. Markus Leweke



Evaluation and Management of Spontaneous Temporal Bone Cerebrospinal Fluid Leaks  

PubMed Central

Spontaneous temporal bone cerebrospinal fluid leak may be defined as a leak without an apparent precipitating cause. These transdural fistulas occur rarely, and diagnosis is predicated upon a high index of suspicion. Leaks have been reported through both middle and posterior fossa defects, although the vast majority involve the middle fossa plate. In a previous study we reported 7 cases of spontaneous temporal bone cerebrospinal fluid leaks, all involving the middle fossa tegmen. Upon further review of these cases and 5 previously unreported cases, the defect was localized to the tegmen tympani in 9 of the total 12 cases. Diagnostic methods are discussed, with the importance of high-resolution computed tomography stressed. The role of contrast cisternography is also evaluated. An outline for surgical management is presented based upon residual hearing and defect location and accessibility. A transmastoid procedure offers the advantage of visualization of both the middle and posterior fossa plates, and this approach can be supplemented with an obliterative procedure when indicated. The middle fossa approach provides optimal exposure of the tegmen plate with less likelihood of ossicular injury when dealing with tegmen tympani defects. Adjuncts to surgical therapy include intrathecal fluorescein dye and continuous postoperative lumbar cerebrospinal fluid drainage. ImagesFigure 1Figure 2Figure 3Figure 4

Pappas, Dennis G.; Hoffman, Ronald A.; Holliday, Roy A.; Hammerschlag, Paul E.; Pappas, Dennis G.; Swaid, Swaid N.



Neoplastic meningitis.  


Neoplastic meningitis is a complication of the CNS that occurs in 3-5% of patients with cancer and is characterised by multifocal neurological signs and symptoms. Diagnosis is problematic because the disease is commonly the result of pleomorphic manifestations of neoplastic meningitis and co-occurrence of disease at other sites. Useful tests to establish diagnosis and guide treatment include MRI of the brain and spine, cerebrospinal fluid (CSF) cytology, and radioisotope CSF flow studies. Assessment of the extent of disease of the CNS is of value because large-volume subarachnoid disease or CSF flow obstruction is prognostically significant. Radiotherapy is an established and beneficial treatment for patients with neoplastic meningitis with large tumour volume including parenchymal brain metastasis, sites of symptomatic disease, or CSF flow block. Because neoplastic meningitis affects the entire neuraxis, chemotherapy treatment can include intra-CSF fluid (either intraventricular or intralumbar) or systemic therapy. Most patients (>70%) with neoplastic meningitis have progressive systemic disease and consequently treatment is palliative and tumour response is of restricted durability. Furthermore, as there is no compelling evidence of a survival advantage with aggressive multimodal treatment, future trials need be done to determine the effect of treatment on quality of life and control of neurological symptoms. PMID:16632315

Gleissner, Beate; Chamberlain, Marc Charles



Endoscopic third ventriculostomy for chronic hydrocephalus after tuberculous meningitis  

Microsoft Academic Search

BackgroundCerebrospinal fluid diversion procedures are indicated in patients with hydrocephalus after tuberculous meningitis (TBM). We present 2 patients with hydrocephalus after TBM who were successfully treated with endoscopic third ventriculostomy (ETV).

Ashish Jonathan; Vedantam Rajshekhar



A chronic fatigue syndrome - related proteome in human cerebrospinal fluid  

PubMed Central

Background Chronic Fatigue Syndrome (CFS), Persian Gulf War Illness (PGI), and fibromyalgia are overlapping symptom complexes without objective markers or known pathophysiology. Neurological dysfunction is common. We assessed cerebrospinal fluid to find proteins that were differentially expressed in this CFS-spectrum of illnesses compared to control subjects. Methods Cerebrospinal fluid specimens from 10 CFS, 10 PGI, and 10 control subjects (50 ?l/subject) were pooled into one sample per group (cohort 1). Cohort 2 of 12 control and 9 CFS subjects had their fluids (200 ?l/subject) assessed individually. After trypsin digestion, peptides were analyzed by capillary chromatography, quadrupole-time-of-flight mass spectrometry, peptide sequencing, bioinformatic protein identification, and statistical analysis. Results Pooled CFS and PGI samples shared 20 proteins that were not detectable in the pooled control sample (cohort 1 CFS-related proteome). Multilogistic regression analysis (GLM) of cohort 2 detected 10 proteins that were shared by CFS individuals and the cohort 1 CFS-related proteome, but were not detected in control samples. Detection of ?1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance (logistic model). The proteins were ?-1-macroglobulin, amyloid precursor-like protein 1, keratin 16, orosomucoid 2 and pigment epithelium-derived factor. Overall, 62 of 115 proteins were newly described. Conclusion This pilot study detected an identical set of central nervous system, innate immune and amyloidogenic proteins in cerebrospinal fluids from two independent cohorts of subjects with overlapping CFS, PGI and fibromyalgia. Although syndrome names and definitions were different, the proteome and presumed pathological mechanism(s) may be shared.

Baraniuk, James N; Casado, Begona; Maibach, Hilda; Clauw, Daniel J; Pannell, Lewis K; Hess S, Sonja



Overton's Rule Helps To Estimate the Penetration of Anti-Infectives into Patients' Cerebrospinal Fluid  

PubMed Central

In 1900, Ernst Overton found that the entry of anilin dyes through the cell membranes of living cells depended on the lipophilicity of the dyes. The brain is surrounded by barriers consisting of lipid layers that possess several inward and outward active transport systems. In the absence of meningeal inflammation, the cerebrospinal fluid (CSF) penetration of anti-infectives in humans estimated by the ratio of the area under the concentration-time curve (AUC) in CSF (AUCCSF) to that in serum (AUCCSF/AUCS) correlated positively with the lipid-water partition coefficient at pH 7.0 (log D) (Spearman's rank correlation coefficient rS = 0.40; P = 0.01) and negatively with the molecular mass (MM) (rS = ?0.33; P = 0.04). The ratio of AUCCSF to the AUC of the fraction in serum that was not bound (AUCCSF/AUCS,free) strongly correlated with log D (rS = 0.67; P < 0.0001). In the presence of meningeal inflammation, AUCCSF/AUCS also correlated positively with log D (rS = 0.46; P = 0.002) and negatively with the MM (rS = ?0.37; P = 0.01). The correlation of AUCCSF/AUCS,free with log D (rS = 0.66; P < 0.0001) was as strong as in the absence of meningeal inflammation. Despite these clear correlations, Overton's rule was able to explain only part of the differences in CSF penetration of the individual compounds. The site of CSF withdrawal (lumbar versus ventricular CSF), age of the patients, underlying diseases, active transport, and alterations in the pharmacokinetics by comedications also appeared to strongly influence the CSF penetration of the drugs studied.

Djukic, Marija; Munz, Martin; Sorgel, Fritz; Holzgrabe, Ulrike; Eiffert, Helmut



Cerebrospinal fluid pleocytosis in febrile infants 1-90 days with urinary tract infection.  


Sterile cerebrospinal fluid pleocytosis occurs in febrile infants with urinary tract infection. Coinfection with enterovirus is a possible cause. We evaluated 57 infants with urinary tract infection and cerebrospinal fluid pleocytosis. All had enterovirus testing by polymerase chain reaction. An explanation for pleocytosis was determined for 24 infants (42%). Enterovirus infection was detected in 4 and is an uncommon cause of cerebrospinal fluid pleocytosis in infants with urinary tract infection. PMID:23584580

Doby, Elizabeth H; Stockmann, Chris; Korgenski, E Kent; Blaschke, Anne J; Byington, Carrie L



Posttraumatic delayed cranio-orbital cerebrospinal fluid leakage: case report.  


A 56-year-old man sustained subarachnoid haemorrhage, skull base fracture and multiple facial fractures in a traffic accident. Two weeks later, the patient developed a subperiosteal fluid collection into the orbit of the right side presenting with a progressive proptosis and an increased intraocular pressure. We performed drainage of the fluid on the superior part of the right orbit, followed by a surgical reduction of the facial fractures. The patient had no exophthalmos any longer, whose intraocular pressure was normalised. In conclusion, our case indicates that careful monitoring of clinical signs and a follow-up radiography would be mandatory for patients with craniocerebral trauma despite a lack of the definite symptoms. Clinicians should consider the possibility that the cerebrospinal fluid (CSF) leakage into the orbit might occur in these patients. PMID:22959849

Rha, Eun Young; Kim, Ji Hwan; Byeon, Jun Hee



Chicken cerebrospinal fluid: normal composition and response to insulin administration  

PubMed Central

1. With the exception of Na, K and Cl clear cerebrospinal fluid (c.s.f.) obtained from chickens varying in age from 6 weeks to 2 years did not reveal significant alterations in composition as could be related to age per se. 2. Considerably higher levels of total protein and glucose are found in chicken c.s.f. than are found in mammalian fluid; slightly more chloride is found in chicken than most mammalian c.s.f.'s. 3. Intravenous beef insulin depressed chicken cerebrospinal fluid glucose levels; insulin placed intracisternally had no effect on the avian glycogen body glycogen content indicating that c.s.f. glucose constancy, with or without glycogen body assistance, is not responsible for the resistance of the chicken to pharmacological doses of insulin. 4. Bovine insulin injected into the cisterna magna of chickens depresses plasma glucose partially by acting over vagal pathways to release endogenous insulin and partially by diffusion across the c.s.f.—blood barrier to exert a peripheral effect.

Anderson, D. K.; Hazelwood, R. L.



Syndrome of spontaneous cerebrospinal fluid hypovolemia: report of six cases.  


Syndrome of spontaneous cerebrospinal fluid hypovolemia (SCH) is a rare cause of new onset headache. We report six cases of SCH presenting with new onset headache. All six cases were females. Acute onset orthostatic headache and neck pain were the chief characteristics of SCH in our cases. The MRI brain showed pachymeningeal gadolinium enhancement in all patients. Spinal extradural CSF collection was demonstrable on MRI in three cases. All cases improved with conservative therapy. High index of clinical suspicion and contrast enhanced MRI brain is the key to accurate diagnosis in the majority of cases. PMID:18040112

Ambady, Prakash; Ahsan Moosa, N V; Anand Kumar, A


Cerebrospinal fluid biomarkers in neurological diseases in children.  


Analysis of cerebrospinal fluid (CSF) biomarkers is an integral part of neurology. Basic CSF biomarkers, such as CSF/serum albumin ratio and CSF cell counts, have been used to diagnose inflammatory and infectious CNS disorders in adults and children for decades. During recent years, however, numerous biomarkers for neuronal and astroglial injury, as well as disease-specific protein inclusions, have been developed for neurodegenerative disorders in adults. The overall aim of this paper is to give an updated overview of some of these biomarkers with special focus on their possible relevance to neurological disorders in children and adolescents. PMID:23026858

Shahim, Pashtun; Månsson, Jan-Eric; Darin, Niklas; Zetterberg, Henrik; Mattsson, Niklas



Spontaneous cerebrospinal fluid rhinorrhea secondary to anterior fossa osteoradionecrosis.  


Osteoradionecrosis (ORN) after radiation therapy of head and neck or brain tumor most often presents in the mandible, followed by the maxillary bone. This case report describes a patient who presented with spontaneous cerebrospinal fluid (CSF) rhinorrhea 12 months after conventional external beam radiotherapy for frontotemporal anaplastic astrocytoma, and was diagnosed with anterior fossa ORN. Osteolysis in the anterior fossa on CT scan confirmed the diagnosis. A prompt temporal muscle graft with pericranial flap seal treated both the ORN and the CSF rhinorrhea, but observation would have been a suitable conservative option if ORN presented without CSF rhinorrhea. PMID:23517671

Hu, Zhebin; Godoy, Bruno L; Zadeh, Gelareh



Phenylacetic acid in human body fluids: high correlation between plasma and cerebrospinal fluid concentration values.  

PubMed Central

In a group of six Parkinsonian patients and 13 "controls" with non-Parkinsonian neurological disease, there was a high correlation between both free and conjugated phenylacetic acid concentrations in plasma and cerebrospinal fluid taken at about the same time. This compound is the major metabolite of phenylethylamine, the production of which may be disturbed in a number of neuropsychiatric illnesses. Thus plasma measurements might be employed clinically to provide an estimate of central changes in phenylethylamine economy. A small but significantly higher proportion of conjugated phenylacetic acid was present in the plasma (but not cerebrospinal fluid) of Parkinsonians compared with controls.

Sandler, M; Ruthven, C R; Goodwin, B L; Lees, A; Stern, G M



Cerebrospinal fluid biomarker candidates of schizophrenia: where do we stand?  


Here, we review the cerebrospinal fluid (CSF) candidate markers with regard to their clinical relevance as potential surrogates for disease activity, prognosis assessment, and predictors of treatment response. We searched different online databases such as MEDLINE and EMBASE for studies on schizophrenia and CSF. Initial studies on cerebrospinal fluid in patients with schizophrenia revealed increased brain-blood barrier permeability with elevated total protein content, increased CSF-to-serum ratio for albumin, and intrathecal production of immunoglobulins in subgroups of patients. Analyses of metabolites in CSF suggest alterations within glutamatergic neurotransmission as well as monoamine and cannabinoid metabolism. Decreased levels of brain-derived neurotrophic factor and nerve growth factor in CSF of first-episode patients with schizophrenia reported in recent studies point to a dysregulation of neuroprotective and neurodevelopmental processes. Still, these findings must be considered as non-specific. A more profound characterization of the particular psychopathological profiles, the investigation of patients in the prodromal phase or within the first episode of schizophrenia promoting longitudinal investigations, implementation of different approaches of proteomics, and rigorous adherence to standard procedures based on international CSF guidelines are necessary to improve the quality of CSF studies in schizophrenia, paving the way for identification of syndrome-specific biomarker candidates. PMID:22173848

Vasic, Nenad; Connemann, Bernhard J; Wolf, Robert C; Tumani, Hayrettin; Brettschneider, Johannes



A comprehensive proteome map of bovine cerebrospinal fluid.  


Cerebrospinal fluid (CSF) is considered as the most promising body fluid target for the discovery of biomarkers for early diagnosis of neurodegenerative diseases such as Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. For the recognition of disease-associated changes in bovine CSF protein patterns, a detailed knowledge of this proteome is a prerequisite. The absence of a high-resolution CSF proteome map prompted us to determine all bovine CSF protein spots that can be visualised on 2-D protein gels. Using state-of-the-art 2-DE technology for proteome mapping of bovine ante mortem CSF combined with sensitive fluorescent protein staining and MALDI-TOF/TOF MS for protein identification, a highly detailed 2-DE map of the bovine CSF proteome was established. Besides the proteins mapped by earlier studies, this map contains 66 different proteins, including 58 which were not annotated in bovine 2-DE CSF maps before. PMID:19921684

Brenn, Anja; Karger, Axel; Skiba, Martin; Ziegler, Ute; Groschup, Martin H



Optical analysis of suspended particles in the cerebrospinal fluid obtained by puncture from patients diagnosed with the disorders of cerebrospinal fluid (CSF) circulation  

NASA Astrophysics Data System (ADS)

The goal of the work was to determine the values of cumulative parameters of the cerebrospinal fluid. Values of the parameters characterise statistical cerebrospinal fluid obtained by puncture from the patients diagnosed due to suspicion of normotensive hydrocephalus. The cerebrospinal fluid taken by puncture for the routine examinations carried out at the patients suspected of normotensive hydrocephalus was analysed. In the paper there are presented results of examinations of several dozens of puncture samples of the cerebrospinal fluid coming from various patients. Each sample was examined under the microscope and photographed in 20 randomly chosen places. On the basis of analysis of the pictures showing the area of 100 x 100?m, the selected cumulative parameters such as count, numerical density, field area and field perimeter were determined for each sample. Then the average value of the parameters was determined as well.

Staro?, Waldemar; Herbowski, Leszek; Gurgul, Henryk



Cerebrospinal fluid tau concentrations in HIV infected patients with suspected neurological disease  

PubMed Central

Objectives: To measure cerebrospinal fluid (CSF) tau in HIV infected patients with acute neurological episodes and to correlate the findings with the type and severity of neurological disease. Methods: CSF tau was prospectively measured in 76 consecutive HIV infected patients admitted to a specialist unit at UCL Hospitals, London, for investigation of acute neurological episodes: the results were compared with the clinical diagnoses. Results: 24 patients had HIV associated dementia complex (HADC), 10 had lymphoma (including four with primary CNS lymphoma), 20 had cerebral infections (including five with CMV encephalitis, five with VZV infection, seven with cryptococcal meningitis, two with toxoplasmosis, and one with progressive multifocal leucoencephalopathy); 22 patients had miscellaneous conditions, including nine with self limiting headache/fever. 62 patients (82%) had normal CSF tau concentration and 14 patients (18%) had elevated tau. In those with HADC, there was no correlation between the degree of dementia or atrophy on magnetic resonance imaging and CSF tau. Elevated CSF tau was associated with poor outcome as six of eight patients who died within 4 weeks of lumbar puncture had elevated tau (p=0.0024, two tailed Fisher's exact test). Conclusions: CSF tau levels are not elevated in the majority of HIV infected patients presenting with acute neurological episodes. CSF tau levels show no correlation with severity of dementia/atrophy on magnetic resonance imaging. Although elevated CSF tau was observed in some patients with conditions causing cerebral necrosis, the finding did not delineate underlying pathology but was associated with poor outcome. Key Words: tau; AIDS; cerebrospinal fluid; dementia; magnetic resonance imaging

Green, A.; Giovannoni, G.; Hall-Craggs, M.; Thompson, E.; Miller, R.





... infections that cause meningitis. Parents of adolescents and students living in college dorms should talk to a doctor about the vaccination. NIH: National Institute of Neurological Disorders and Stroke


Penetration of fusidic acid into human brain tissue and cerebrospinal fluid  

Microsoft Academic Search

Summary Penetration of fusidic acid into brain tissue in six patients and cerebrospinal fluid in seven patients was determined. Tissue samples, taken during surgery revealed drug levels at about 7% of simultaneous serum concentrations. In contrast, cerebrospinal fluid concentrations were below 1% of serum levels. Since serum- and tissue levels of fusidic acid were far above the minimal inhibitory concentration

Th Mindermann; W. Zimmerli; Z. Rajacic; O. Gratzl



Coronary artery bypass surgery in the presence of cerebrospinal fluid rhinorrhea.  


A seventy eight year old male patient was admitted in our hospital with headache, vomiting, irritability and confusion. Initially he was diagnosed as a case of pyogenic encephalitis. Further investigations revealed that patient had cerebrospinal fluid rhinorrhea and coronary artery disease. He successfully underwent coronary artery bypass grafting and cerebrospinal fluid leak repair. PMID:24107697

Rawat, Rajinder Singh; Mehta, Yatin; Trehan, Naresh; Gupta, Aditya


High Blood Pressure Effects on the Blood to Cerebrospinal Fluid Barrier and Cerebrospinal Fluid Protein Composition: A Two-Dimensional Electrophoresis Study in Spontaneously Hypertensive Rats  

PubMed Central

The aim of the present work is to analyze the cerebrospinal fluid proteomic profile, trying to find possible biomarkers of the effects of hypertension of the blood to CSF barrier disruption in the brain and their participation in the cholesterol and ?-amyloid metabolism and inflammatory processes. Cerebrospinal fluid (CSF) is a system linked to the brain and its composition can be altered not only by encephalic disorder, but also by systemic diseases such as arterial hypertension, which produces alterations in the choroid plexus and cerebrospinal fluid protein composition. 2D gel electrophoresis in cerebrospinal fluid extracted from the cistern magna before sacrifice of hypertensive and control rats was performed. The results showed different proteomic profiles between SHR and WKY, that ?-1-antitrypsin, apolipoprotein A1, albumin, immunoglobulin G, vitamin D binding protein, haptoglobin and ?-1-macroglobulin were found to be up-regulated in SHR, and apolipoprotein E, transthyretin, ?-2-HS-glycoprotein, transferrin, ?-1?-glycoprotein, kininogen and carbonic anhidrase II were down-regulated in SHR. The conclusion made here is that hypertension in SHR produces important variations in cerebrospinal fluid proteins that could be due to a choroid plexus dysfunction and this fact supports the close connection between hypertension and blood to cerebrospinal fluid barrier disruption.

Gonzalez-Marrero, Ibrahim; Castaneyra-Ruiz, Leandro; Gonzalez-Toledo, Juan M.; Castaneyra-Ruiz, Agustin; de Paz-Carmona, Hector; Castro, Rafael; Hernandez-Fernaud, Juan R.; Castaneyra-Perdomo, Agustin; Carmona-Calero, Emilia M.



The Choroid Plexuses and the Barriers Between the Blood and the Cerebrospinal Fluid  

Microsoft Academic Search

1. The fluid homeostasis of the brain depends both on the endothelial blood–brain barrier and on the epithelial blood–cerebrospinal fluid (CSF) barrier located at the choroid plexuses and the outer arachnoid membrane.

Malcolm B. Segal



Rifamycin in neonatal flavobacteria meningitis  

Microsoft Academic Search

Three newborn infants with meningitis due to Flavobacterium meningosepticum were treated with rifamycin administered parenterally and directly into the cerebral ventricles. Antibiotic concentrations of blood and cerebrospinal fluid (CSF) were monitored during treatment. There was rapid sterilization of the CSF after this antibiotic. Jaundice was the only toxicity noted. All 3 infants developed hydrocephalus and are shunt dependent. Two of

E L Lee; M J Robinson; M L Thong; S D Puthucheary



Clinical features and prognostic factors in adults with bacterial meningitis  

Microsoft Academic Search

background We conducted a nationwide study in the Netherlands to determine clinical features and prognostic factors in adults with community-acquired acute bacterial meningitis. methods From October 1998 to April 2002, all Dutch patients with community-acquired acute bacterial meningitis, confirmed by cerebrospinal fluid cultures, were prospectively eval- uated. All patients underwent a neurologic examination on admission and at discharge, and outcomes

Diederik van de Beek; Jan de Gans; Lodewijk Spanjaard; Martijn Weisfelt; Johannes B. Reitsma; Marinus Vermeulen



Cerebrospinal fluid biopterin is decreased in Alzheimer's disease.  


Tetrahydrobiopterin is the cofactor in the hydroxylation of phenylalanine, tyrosine, and tryptophan leading to the eventual synthesis of the monoaminergic neurotransmitters, dopamine, norepinephrine, and serotonin, respectively. Total biopterin (90% of which is in the tetrahydro form) was measured in cerebrospinal fluid (CSF) and plasma of 30 patients with Alzheimer's disease and of 19 healthy controls. Plasma and CSF biopterin concentrations were not significantly correlated, but the mean CSF biopterin concentration in patients with Alzheimer's disease was significantly less than in age-matched controls, 13.5 pmol/mL as compared with 18.9 pmol/mL. The CSF biopterin concentration was not correlated with ventricular volume, as estimated by quantitative computed tomography, nor with the severity of dementia, as measured by various cognitive tests. The results suggest that a central biopterin deficiency exists in Alzheimer's disease. PMID:2428341

Kay, A D; Milstien, S; Kaufman, S; Creasey, H; Haxby, J V; Cutler, N R; Rapoport, S I



[A case report: a repeated cerebrospinal fluid otorrhea].  


Cerebrospinal fluid (CSF) otorrhea, leakage of CSF through the ear structures, may occur from a traumatic or operative defect in the skull, tumor, cholesteatoma, or congenital anomalies. A case of repeated CSF otorrhea is uncommon. In this report, we presented a case of a repeated CSF otorrhea which occurred a decade after the first middle ear surgery for chronic otitis media. The first CSF leakage, which might have been due to bone defects in the tegmen at the first middle ear sutgery, was surgically repaired using a transmastoid approach. However, CSF leakage with a meningoencephalocele occurred again 8 years after our first surgery for the CSF and the fistula was repaired using a transmiddle cranial fossa approach. Although 2 years have passed since the surgery, the CSF leakage has not recurred. PMID:23678672

Arai, Yasuhiro; Sakuma, Naoko; Sano, Daisuke; Takahashi, Masahiro; Matsuda, Hideki; Ikoma, Ryo; Sakane, Sayaka; Niwa, Kazutomo; Cho, Iemasa; Ishitoya, Junichi



Spontaneous Cerebrospinal Fluid Leaks Originating from Multiple Skull Base Defects  

PubMed Central

Spontaneous cerebrospinal fluid (CSF) leaks of temporal bone origin are more prevalent than once believed. Twenty-eight of the 61 cases documented in the world literature have been reported since 1992. All but four of these cases involved unilateral defects. The authors have previously reported experiences with 12 cases, with the vast majority of defects localized to the tegmen tympani. These patients also had demonstrated a single area of bone and dural dehiscence. We report two additional cases of spontaneous CSF leak originating from multiple/distant skull base defects. As in previously reported multisite cases, one of our patients demonstrated an elevated opening pressure on lumbar puncture. Significant time intervals existed between leak site presentations, which emphasizes the importance of careful follow-up for treated patients. Potential etiologies and associated factors are also discussed. This patient subset contributes another dimension to the evolving natural history of spontaneous CSF leakage. ImagesFigure 1Figure 2Figure 3

Pappas, Dennis G.; Pappas, Dennis G.; Hoffman, Ronald A.; Harris, Steven D.



Cerebrospinal Fluid Otorrhea Treated by Extended Subtotal Petrosectomy with Obliteration  

PubMed Central

Extended subtotal petrosectomy as a treatment for stubborn cerebrospinal fluid (CSF) otorrhea is presented. Nine patients were successfully operated on by this technique, all previously having undergone surgery for brain or base of skull lesions, other interventions used had failed to seal the fistula. The retrosigmoid cells, facial cells, and internal auditory canal were found in our study to be the most commonly involved during pervious neurosurgery and so constituted the usual path for CSF leakage. Total exenteration of middle ear and mastoid cell tracts, skeletization of sigmoid sinus, jugular bulb and facial nerve, drilling out of the semicircular canals, vestibulum, and cochlea, and skeletization of the internal auditory canal are the main steps of this approach.

Kronenberg, J.; Findler, G.; Braham, J.



Seizures with decreased levels of pyridoxal phosphate in cerebrospinal fluid.  


Although pyridoxine-dependent seizures have been reported for decades, pyridoxamine phosphate oxidase deficiency has only been recently described. Pyridoxamine phosphate oxidase (PNPO) is one of a series of enzymes involved in converting pyridoxine to pyridoxal 5'-phosphate, the biologically active form of pyridoxine. PNPO deficiency is associated with decreased levels of pyridoxal 5'-phosphate in CSF, as well as epilepsy. We describe four children up to 16 years of age with intractable seizures who all had low cerebrospinal fluid (CSF) levels of pyridoxal 5'-phosphate. Only one of the four children possessed a genetic alteration, a novel homozygous variant in exon one of the PNPO gene. Three of four, however, showed at least some clinical improvement with pyridoxal 5'-phosphate supplementation. Low CSF pyridoxal 5'-phosphate levels, although considered a diagnostic biomarker for PNPO deficiency, lack specificity and may result from multiple other causes. Genetic testing and CSF evaluation, along with clinical response are all necessary for accurate diagnosis. PMID:23419474

Goyal, Monisha; Fequiere, Pierre R; McGrath, Tony M; Hyland, Keith



Oligoclonal immunoglobulin G in cerebrospinal fluid of myasthenia gravis patients.  


Immunoglobulin G (IgG) band patterns were investigated in cerebrospinal fluid (CSF) from 19 patients with myasthenia gravis (MG) in a search for abnormalities indicating central nervous system (CNS) involvement in this disorder. Using the isoelectric focusing (IEF) technique and antiserum immunoblotting against IgG, we found no evidence of the presence of oligoclonal IgG in CSF from most of MG patients. In 2 cases, the positive findings of oligoclonal IgG in CSF may have reflected a manifestation of an associated disease, which has already been associated with immune abnormalities within the CNS. Further investigations with more sophisticated techniques are required to give additional insight into humoral immune events within the CNS in MG patients. PMID:2112820

Mavra, M; Apostolski, S; Nikolic, J; Thompson, E J



Confounding Factors Influencing Amyloid Beta Concentration in Cerebrospinal Fluid  

PubMed Central

Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of ?-amyloid (A?42). However, a high discrepancy between different centers in measured A?42 levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured A?42 level. Methods. Aliquots of CSF samples were either treated differently prior to A?42 measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF A?42 levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted.

Bjerke, Maria; Portelius, Erik; Minthon, Lennart; Wallin, Anders; Anckarsater, Henrik; Anckarsater, Rolf; Andreasen, Niels; Zetterberg, Henrik; Andreasson, Ulf; Blennow, Kaj



Confounding factors influencing amyloid Beta concentration in cerebrospinal fluid.  


Background. Patients afflicted with Alzheimer's disease (AD) exhibit a decrease in the cerebrospinal fluid (CSF) concentration of the 42 amino acid form of beta-amyloid (Abeta(42)). However, a high discrepancy between different centers in measured Abeta(42) levels reduces the utility of this biomarker as a diagnostic tool and in monitoring the effect of disease modifying drugs. Preanalytical and analytical confounding factors were examined with respect to their effect on the measured Abeta(42) level. Methods. Aliquots of CSF samples were either treated differently prior to Abeta(42) measurement or analyzed using different commercially available xMAP or ELISA assays. Results. Confounding factors affecting CSF Abeta(42) levels were storage in different types of test tubes, dilution with detergent-containing buffer, plasma contamination, heat treatment, and the origin of the immunoassays used for quantification. Conclusion. In order to conduct multicenter studies, a standardized protocol to minimize preanalytical and analytical confounding factors is warranted. PMID:20798852

Bjerke, Maria; Portelius, Erik; Minthon, Lennart; Wallin, Anders; Anckarsäter, Henrik; Anckarsäter, Rolf; Andreasen, Niels; Zetterberg, Henrik; Andreasson, Ulf; Blennow, Kaj



Increased cerebrospinal fluid cAMP levels in Alzheimer's disease.  


Since increasing evidence suggests that upregulation of the cAMP-second messenger system may be implicated in Alzheimer's disease neurodegeneration, we have compared the cAMP and cGMP levels in cerebrospinal fluid (CSF) from patients with dementia of the Alzheimer type (DAT, n=10) with those from nondemented age-matched controls (n=10). Our results show that cAMP levels, but not cGMP, are significantly (p<0.01) elevated in CSF from patients with DAT compared to those from nondemented controls. Moreover, a linear regression analysis demonstrated a significant correlation (r=0.62; p<0.01) between cAMP and tau protein levels in CSF when controls and patients with DAT were studied together. These results suggest that upregulation of cAMP-signaling pathway is implicated in Alzheimer's disease physiopathology. PMID:10556645

Martínez, M; Fernández, E; Frank, A; Guaza, C; de la Fuente, M; Hernanz, A



Endoscopic repair of cerebrospinal fluid rhinorrhoea in a developing country.  


The objectives of the study was to determine the causes and outcome of endoscopic repair of cerebrospinal fluid (CSF) leak in a developing country. A total of five patients were recruited in the study. The age of patients ranged from 8 to 65 years. Four patients were male and one was female. In two cases of iatrogenic injury, the first was in the sphenoid sinus. The second was following functional endoscopic sinus surgery (FESS). Fascia lata was used to repair all cases. Beriplast was used as sealing agent in four cases and clotted blood was used in remaining case. Despite the small number, CSF rhinor rhoea was resolved in all cases. The patients were followed up for 2.5 to 6.5 years. Endoscopic repair is a viable option even in developing countries. It is cost effective and has a very low morbidity rate with no mortality at all. PMID:23139989

Akhter, Saeed; Zia, Sadaf; Zafar, Rafay



Cerebrospinal Fluid Proteomics Reveals Potential Pathogenic Changes in the Brains of SIV-infected Monkeys  

PubMed Central

The HIV-1-associated neurocognitive disorder occurs in approximately one-third of infected individuals. It has persisted in the current era of anti-retroviral therapy, and its study is complicated by the lack of biomarkers for this condition. Since the cerebrospinal fluid is the most proximal biofluid to the site of pathology, we studied the cerebrospinal fluid in a nonhuman primate model for HIV-1-associated neurocognitive disorder. Here we present a simple and efficient liquid chromatography coupled mass spectrometry based proteomics approach that utilizes small amounts of cerebrospinal fluid. First, we demonstrate the validity of the methodology using human cerebrospinal fluid. Next, using the simian immunodeficiency virus infected monkey model, we show its efficacy in identifying proteins such as alpha-1-antitrypsin, complement C3, hemopexin, IgM heavy chain and plasminogen, whose increased expression is linked to disease. Finally, we find that the increase in cerebrospinal fluid proteins is linked to increased expression of their genes in the brain parenchyma, revealing that the cerebrospinal fluid alterations identified reflect changes in the brain itself and not merely leakage of the blood-brain or blood- cerebrospinal fluid barriers. This study reveals new central nervous system alterations in lentivirus-induced neurological disease, and this technique can be applied to other systems in which limited amounts of biofluids can be obtained.

Pendyala, Gurudutt; Trauger, Sunia A.; Kalisiak, Ewa; Ellis, Ronald J.; Siuzdak, Gary; Fox, Howard S.



Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid.  


Cerebrospinal fluid has shown itself to be an essential brain component during development. This is particularly evident at the earliest stages of development where a lot of research, performed mainly in chick embryos, supports the evidence that cerebrospinal fluid is involved in different mechanisms controlling brain growth and morphogenesis, by exerting a trophic effect on neuroepithelial precursor cells (NPC) involved in controlling the behaviour of these cells. Despite it being known that cerebrospinal fluid in mammals is directly involved in corticogenesis at fetal stages, the influence of cerebrospinal fluid on the activity of NPC at the earliest stages of brain development has not been demonstrated. Here, using "in vitro" organotypic cultures of rat embryo brain neuroepithelium in order to expose NPC to or deprive them of cerebrospinal fluid, we show that the neuroepithelium needs the trophic influence of cerebrospinal fluid to undergo normal rates of cell survival, replication and neurogenesis, suggesting that NPC are not self-sufficient to induce their normal activity. This data shows that cerebrospinal fluid is an essential component in chick and rat early brain development, suggesting that its influence could be constant in higher vertebrates. PMID:19540909

Martin, C; Alonso, M I; Santiago, C; Moro, J A; De la Mano, A; Carretero, R; Gato, A



Tick-borne encephalitis is associated with low levels of interleukin-10 in cerebrospinal fluid  

PubMed Central

Tick-borne encephalitis (TBE) is associated with higher morbidity and induces a stronger intrathecal immune activation than most other viral induced meningo-encephalitis. The aim of this study was to investigate cytokine concentrations in cerebrospinal fluid (CSF) and serum in relation to aetiology and clinical course. Cytokines were analysed by Enzyme-linked Immuno Assay (ELISA) from 44 patients with TBE and from 36 patients with aseptic meningo-encephalitis of other aetiology (non-TBE). Significantly increased CSF levels of Interferon-? (IFN-?), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Interleukin-1 receptor antagonist (IL-1ra), and soluble CD8 receptor (sCD8) were detected in both cohorts. Tumour necrosis factor-? (TNF-? showed low levels or was not detected in CSF in any group in the acute stage. However, the CSF levels of IL-10 were significantly lower in TBE than in non-TBE cases 0–6 days after onset of encephalitis. The TBE patients with encephalitis had significantly lower IL-10 CSF levels later in the clinical course (day 7–18) than TBE patients with meningeal disease. Increased IFN-? production, but low IL-10 secretion, may be of pathophysiological significance in TBE.

Gunther, Goran; Haglund, Mats; Lindquist, Lars; Forsgren, Marianne; Andersson, Jan; Andersson, Birger; Skoldenberg, Birgit



Gelatinase activity of matrix metalloproteinases in the cerebrospinal fluid of various patient populations.  


We have studied the enzymatic gelatinolytic activity of matrix metalloproteinases (MMPs) present in cerebrospinal fluid (CSF) of samples obtained from 67 individuals, twenty-one nonneurological patients (considered controls) and 46 subjects with various neurological disorders e.g., vascular lesions, demyelination, inflammatory, degenerative and prion diseases. Biochemical characterization of MMPs, a family of neutral proteolytic enzymes involved in extracellular matrix modeling, included determination of substrate specificity and Ca+2 dependency, as well as the effects of protease inactivators, carboxylic and His (histidine) residue modifiers, and antibiotics. Whereas all CSF samples expressed MMP-2 (gelatinase A) activity, it corresponded in most cases (normal and pathological samples) to its latent form (proenzyme; pMMP-2). In general, inflammatory neurological diseases (especially meningitis and neurocisticercosis) were associated with the presence of a second enzyme, MMP-9 (or gelatinase B). Whereas MMP-9 was found in the CSF of every tropical spastic paraparesis patient studied, its presence in samples from individuals with vascular lesions was uncommon. Patients blood-brain barrier damage was ascertained by determining total CSF protein content using both, the conventional polyacrylamide gel electrophoresis procedure under denaturing conditions and capillary zone electrophoresis. PMID:10604277

Valenzuela, M A; Cartier, L; Collados, L; Kettlun, A M; Araya, F; Concha, C; Flores, L; Wolf, M E; Mosnaim, A D



Cysticercus Antigens in Cerebrospinal Fluid Samples from Patients with Neurocysticercosis  

PubMed Central

Antigens were detected in cerebrospinal fluid (CSF) samples from patients with neurocysticercosis (NC) by enzyme-linked immunosorbent assay (ELISA) using polyclonal sera of rabbit anti-Taenia solium cysticerci (anti-Tso) and anti- Taenia crassiceps cysticerci vesicular fluid (anti-Tcra or anti-Tcra <30 kDa). A group of NC patients (n = 174) were studied (NC), including 40 patients in different phases of the disease. ELISAs carried out with the anti-Tso, anti-Tcra, and anti-Tcra <30 kDa showed sensitivities of 81.2, 90, and 95.8% and specificities of 82, 98, and 100%, respectively. The 14- and 18-kDa low-molecular-weight peptides were only detected in CSF samples from patients with NC by immunoblotting with anti-Tso and anti-Tcra sera. Because of the importance of the diagnosis and prognosis of cysticercosis, the detection of antigens may contribute as an additional marker to the study and clarification of the parasite-host relationship.

Pardini, Alessandra Xavier; Vaz, Adelaide Jose; Machado, Luis Dos Ramos; Livramento, Jose Antonio



Differentiation of communicating hydrocephalus and presenile dementia by continuous recording of cerebrospinal fluid pressure.  

PubMed Central

Continuous monitoring of the cerebrospinal fluid pressure and observation of the pressure during intrathecal infusion of normal saline at two rates were performed in patients with communicating hydrocephalus and cerebral atrophy of other causes. Constant or temporarily increased cerebrospinal fluid pressure was observed only in communicating hydrocephalus. Reduction of intracranial pressure by a ventriculoatrial shunt was associated with clinical improvement. The intrathecal infusion test was capable of detecting reduced absorption of cerebrospinal fluid if more than one infusion rate was employed. Using both tests it is easier to determine which patients with communicating hydrocephalus should be treated with a shunt operation. Images

Hartmann, A; Alberti, E



Review of "Proteins of the Cerebrospinal Fluid" (2nd Edition) by Edward J. Thompson  

PubMed Central

This book on cerebrospinal fluid (CSF) proteins is primarily focused on immunoglobulins. The book was written as an extension of a meeting on multiple sclerosis to provide a more extensive consideration of the CSF.

Connor, James R



Human herpesvirus 8 DNA in the cerebrospinal fluid of a patient with sensory impairment.  


This note reports the finding of human herpes virus 8 DNA in the cerebrospinal fluid of a woman with sensory impairment correlated with a basal disease suspected to be multiple sclerosis. PMID:11718379

Portolani, M; Sabbatini, A M; Gennari, W; Beretti, F; Greco, G; Santangelo, M



The Effect of Dexamethasone on the Formation Rate of Cerebrospinal Fluid in Monkeys.  

National Technical Information Service (NTIS)

A standard ventriculocisternal perfusion technique was used to determine what effect a single large intravenous dose of dexamethasone would have on cerebrospinal fluid (CSF) formation rate in the rhesus monkey over a 4-hour period. Three monkeys received ...

A. N. Martins A. Ramirez L. S. Solomon G. M. Wiese



Autoradiographische Untersuchungen an Liquorzellen. (Autoradiographic investigations of cells from the cerebrospinal fluid).  

National Technical Information Service (NTIS)

A total of 155 samples of cerebrospinal fluid obtained from 61 patients were subjected to cytological examination and incubated together with /sub 3//sup 1/H-thymidine. Radioactive labelling was thus achieved for lymphocytes, monocytes and tumour cells. T...

W. Thamm



Cellulose Acetate Electrophoresis of Cerebrospinal Fluid Proteins with Normal Values of 135 Persons.  

National Technical Information Service (NTIS)

A study on cellulose acetate electrophoresis of cerebrospinal fluid (CSF) proteins is reported. Two methods are used for concentration, acetone precipitation and sephadex dialysis with slight modifications. They are both considered to be clinically valuab...



Investigation of Cerebrospinal Fluid Shunt Valves: Test Results for Twenty-Five Valves.  

National Technical Information Service (NTIS)

The report describes the result of an investigation of design and implement a bench test for cerebrospinal fluid shunt valves. The original contract was extended for the purpose of utilizing the bench test to analyze 25 additional commercially available h...

H. D. Keith R. L. Lu C. C. Fu S. Shao



Study on spontaneous cerebrospinal fluid rhinorrhoea: its aetiology and management.  


The aim of this study was to identify the common features in a study group of patients with spontaneous cerebrospinal fluid (CSF) rhinorrhoea, to develop a hypothesis to explain the cause of this condition and to investigate the outcome of surgical techniques adopted to repair the leak. In this retrospective study the authors have reviewed all the cases of spontaneous CSF leaks attending and receiving treatment from the otolaryngology department of Queen Elizabeth Hospital, Birmingham, from 1992 to 2002. Of 34 patients with CSF leaks, 15 were spontaneous in nature and formed the study group. Of these 15 patients, 14 were female; with ages ranging from 37 to 70 years and a median age of 50 years. All the female patients were overweight with a body mass index (BMI) >24.9 and, of these, nine were considered obese with a BMI >30. It was attempted to identify common factors in the study group and it was evident that female sex, obesity and age played a key role in this condition. The follow-up period ranged from two to 98 months. Thirteen patients were asymptomatic but two patients remained symptomatic, one of these despite repeated surgical intervention. PMID:15807955

Dunn, C J; Alaani, A; Johnson, A P



Proteomics Analysis of Perilymph and Cerebrospinal Fluid in Mouse  

PubMed Central

Objectives Proteins in perilymph may alter the delivery profile of implantable intracochlear drug delivery systems through biofouling. Knowledge of protein composition will help anticipate interactions with delivered agents. Study Design Analysis of mouse perilymph. Methods Protein composition of perilymph and cerebrospinal fluid (CSF) was analyzed using a capillary liquid chromatography-mass spectrometry-based iTRAQ quantitative proteomics approach. We searched against a mouse subset of the Uniprot FASTA protein database. We sampled perilymph from the apex of the mouse cochlea to minimize CSF contamination. Results More than 50 explicit protein isoforms were identified with very high confidence. iTRAQ reporter ions allowed determination of relative molar amounts of proteins between perilymph and CSF. Protein in perilymph was almost three times more concentrated than in CSF. More than one-third of the proteins in perilymph comprised protease inhibitors, with serpins being the predominant group. Apolipoproteins constituted 16%. Fifteen percent of the proteins were enzymes. Albumin was the most abundant single protein (14%). Proteins with relatively high perilymph/CSF ratios included broad-spectrum protease inhibitors and apolipoproteins. Discussion Some proteins found in perilymph, such as albumin and HMW kininogen, have been implicated in biofouling through adsorption to device materials. The relatively large quantities of apolipoprotein and albumin may serve as a reservoir for acidic and lipophillic drugs. Alpha-2-glycoprotein can bind basic drugs. Conclusions Perilymph is similar in protein composition to CSF, though amounts are 2.8 times higher. Protease inhibitors comprise the largest category of proteins.

Leary Swan, Erin E.; Peppi, Marcello; Chen, Zhiqiang; Green, Karin M.; Evans, James E.; McKenna, Michael J.; Mescher, Mark J.; Kujawa, Sharon G.; Sewell, William F.



Cerebrospinal Fluid Biomarkers in Idiopathic Normal Pressure Hydrocephalus  

PubMed Central

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau181, A?42, NFL, TNF-?, TGF?1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result—that is, their gait symptoms improved; 9?patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-? concentration was low in iNPH patients.

Leinonen, Ville; Menon, Lata G.; Carroll, Rona S.; Dello Iacono, Donna; Grevet, Jeremy; Jaaskelainen, Juha E.; Black, Peter M.



Cerebrospinal fluid biomarkers in idiopathic normal pressure hydrocephalus.  


The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau(181), A?(42), NFL, TNF-?, TGF?1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result-that is, their gait symptoms improved; 9?patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-? concentration was low in iNPH patients. PMID:21660204

Leinonen, Ville; Menon, Lata G; Carroll, Rona S; Dello Iacono, Donna; Grevet, Jeremy; Jääskeläinen, Juha E; Black, Peter M



Brain ventricular volume and cerebrospinal fluid biomarkers of Alzheimer's disease  

PubMed Central

The frequent co-occurrence of Alzheimer disease (AD) pathology in patients with normal pressure hydrocephalus suggests a possible link between ventricular dilation and AD. If enlarging ventricles serve as a marker of faulty cerebrospinal fluid (CSF) clearance mechanisms, then a relationship may be demonstrable between increasing ventricular volume and decreasing levels of amyloid beta peptide (A?) in CSF in preclinical and early AD. CSF biomarker data (A?, tau, and phosphorylated tau) as well as direct measurements of whole brain and ventricular volumes were obtained from the Alzheimer's Disease Neuroimaging Initiative dataset. The ratio of ventricular volume to whole brain volume was derived as a secondary independent measure. Baseline data were used for the group analyses of 288 subjects classified as being either normal (n=87), having the syndrome of mild cognitive impairment (n=136), or mild AD (n=65). Linear regression models were derived for each biomarker as the dependent variable, using the MRI volume measures and age as independent variables. For controls, ventricular volume was negatively associated with CSF A? in APOE ?4 positive subjects. A different pattern was seen in AD subjects, in whom ventricular volume was negatively associated with tau, but not A? in ?4 positive subjects. Increased ventricular volume may be associated with decreased levels of CSF A? in preclinical AD. The basis for the apparent effect of APOE ?4 genotype on the relationship of ventricular volume to A? and tau levels is unknown, but could involve altered CSF-blood-brain barrier function during the course of disease.

Ott, Brian R.; Cohen, Ronald A.; Gongvatana, Assawin; Okonkwo, Ozioma C.; Johanson, Conrad E.; Stopa, Edward G.; Donahue, John E.; Silverberg, Gerald D.



Cerebrospinal fluid rhinorrhea: An institutional perspective from Pakistan  

PubMed Central

Background: The management of cerebrospinal fluid (CSF) rhinorrhea has evolved over the last two decades. We present here a review of our 11-year data on CSF rhinorrhea and its management at a tertiary care hospital in a developing country, with particular reference to the diagnosis, surgical management and outcome of the disease. Methods: The medical charts of all patients with a diagnosis of CSF rhinorrhea over an 11-year period were reviewed. The etiology of CSF rhinorrhea was classified into three categories: spontaneous, iatrogenic and traumatic. All the patients were divided into three categories based on the type of management as conservative, intracranial and transnasal endoscopic groups. Results: A total of 43 patients fulfilled our inclusion criteria and were included in the final analysis. Eleven of the 43 patients were managed conservatively, while 22 underwent intracranial repairs; 10 patients had transnasal endoscopic repairs. The primary success rate for the transnasal approach was 70% compared to 86% for the intracranial repair. Blood loss, special care unit (SCU) stay and total cost were found to be significantly less in the transnasal endoscopic group. Computed tomography (CT) cisternography was found to have the highest sensitivity and specificity. Further, no postoperative complications were found in the transnasal endoscopic group, while five patients from the intracranial group developed various complications. Conclusions: We conclude that the transnasal endoscopic approach has comparable success rates with the intracranial approach and significantly lower morbidity.

Tahir, Muhammad Zubair; Khan, Muhammad Babar; Bashir, Muhammad Umair; Akhtar, Shabbir; Bari, Ehsan



Raltegravir Cerebrospinal Fluid Concentrations in HIV-1 Infection  

PubMed Central

Introduction Raltegravir is an HIV-1 integrase inhibitor currently used in treatment-experienced HIV-1-infected patients resistant to other drug classes. In order to assess its central nervous system penetration, we measured raltegravir concentrations in cerebrospinal fluid (CSF) and plasma in subjects receiving antiretroviral treatment regimens containing this drug. Methods Raltegravir concentrations were determined by liquid chromatography tandem mass spectrometry in 25 paired CSF and plasma samples from 16 HIV-1-infected individuals. The lower limit of quantitation was 2.0 ng/ml for CSF and 10 ng/ml for plasma. Results Twenty-four of the 25 CSF samples had detectable raltegravir concentrations with a median raltegravir concentration of 18.4 ng/ml (range, <2.0–126.0). The median plasma raltegravir concentration was 448 ng/ml (range, 37–5180). CSF raltegravir concentrations correlated with CSF:plasma albumin ratios and CSF albumin concentrations. Conclusions Approximately 50% of the CSF specimens exceeded the IC95 levels reported to inhibit HIV-1 strains without resistance to integrase inhibitors. In addition to contributing to control of systemic HIV-1 infection, raltegravir achieves local inhibitory concentrations in CSF in most, but not all, patients. Blood-brain and blood-CSF barriers likely restrict drug entry, while enhanced permeability of these barriers enhances drug entry.

Yilmaz, Aylin; Gisslen, Magnus; Spudich, Serena; Lee, Evelyn; Jayewardene, Anura; Aweeka, Francesca; Price, Richard W.



Cerebrospinal fluid apolipoprotein E levels in subacute sclerosing panencephalitis.  


Neurofibrillary tangles (NFTs) have been shown in 20% of subacute sclerosing panencephalitis (SSPE) cases. NFTs contain paired helical filaments formed by hyperphosphorylated tau. The intraneuronal tau metabolism and the rate of formation of paired helical filaments can be regulated by interactions between tau and isoforms of Apolipoprotein E (Apo E). Tau binds in vitro to Apo E3, interferes with the hyperphosphorylation of tau and may reduce the formation of NFTs. We investigated cerebrospinal fluid (CSF) Apo E levels in SSPE (n=37) and age-matched control (n=38) groups. The median level of total Apo E and Apo E4 were lower in the SSPE than the control group (p<0.001 and p=0.002). On the other hand, median Apo E3 level (0.28±0.23 ?g/ml) was higher in the SSPE group (p<0.001). Such elevated levels of ApoE3 might play a role in controlling the formation of NFTs in SSPE. Because NFT-associated neurodegeneration is a slow process, comparison of the long-term clinical course of SSPE cases with high and low Apo E3 levels might provide further understanding or the role of these molecules in this disease, and help the planning of neuroprotective treatment. PMID:21788110

Yüksel, Deniz; Ichiyama, Takashi; Yilmaz, Deniz; Anlar, Banu



Two-compartment model of radioimmunotherapy delivered through cerebrospinal fluid  

PubMed Central

Purpose Radioimmunotherapy (RIT) using 131I-3F8 injected into cerebrospinal fluid (CSF) was a safe modality for the treatment of leptomeningeal metastases (JCO, 25:5465, 2007). A single-compartment pharmacokinetic model described previously (JNM 50:1324, 2009) showed good fitting to the CSF radioactivity data obtained from patients. We now describe a two-compartment model to account for the ventricular reservoir of 131I-3F8 and to identify limiting factors that may impact therapeutic ratio. Methods Each parameter was examined for its effects on (1) the area under the radioactivity concentration curve of the bound antibody (AUC[CIAR]), (2) that of the unbound antibody AUC[CIA], and (3) their therapeutic ratio (AUC [CIAR]/AUC[CIA]). Results Data fitting showed that CSF kBq/ml data fitted well using the two-compartment model (R=0.95±0.03). Correlations were substantially better when compared to the one-compartment model (R=0.92±0.11 versus 0.77±0.21, p=0.005). In addition, we made the following new predictions: (1) Increasing immunoreactivity of 131I-3F8 from 10% to 90% increased both (AUC[CIAR]) and therapeutic ratio ([AUC[CIAR]/AUC[CIA

He, Ping; Kramer, Kim; Smith-Jones, Peter; Zanzonico, Pat; Humm, John; Larson, Steven M.



Cerebrospinal fluid biomarkers in human genetic transmissible spongiform encephalopathies.  


The 14-3-3 protein test has been shown to support the clinical diagnosis of sporadic Creutzfeldt-Jakob disease (CJD) when associated with an adequate clinical context, and a high differential potential for the diagnosis of sporadic CJD has been attributed to other cerebrospinal fluid (CSF) proteins such as tau protein, S100b and neuron specific enolase (NSE). So far there has been only limited information available about biochemical markers in genetic transmissible spongiform encephalopathies (gTSE), although they represent 10-15% of human TSEs. In this study, we analyzed CSF of 174 patients with gTSEs for 14-3-3 (n = 166), tau protein (n = 78), S100b (n = 46) and NSE (n = 50). Levels of brain-derived proteins in CSF varied in different forms of gTSE. Biomarkers were found positive in the majority of gCJD (81%) and insert gTSE (69%), while they were negative in most cases of fatal familial insomnia (13%) and Gerstmann-Sträussler-Scheinker syndrome (10%). Disease duration and codon 129 genotype influence the findings in a different way than in sporadic CJD. PMID:19444528

Ladogana, Anna; Sanchez-Juan, Pascual; Mitrová, Eva; Green, Alison; Cuadrado-Corrales, Natividad; Sánchez-Valle, Raquel; Koscova, Silvia; Aguzzi, Adriano; Sklaviadis, Theodoros; Kulczycki, Jerzy; Gawinecka, Joanna; Saiz, Albert; Calero, Miguel; van Duijn, Cornelia M; Pocchiari, Maurizio; Knight, Richard; Zerr, Inga



Soluble CD146 in cerebrospinal fluid of active multiple sclerosis.  


The soluble form of CD146 has been reported to be present in various inflammatory diseases and displays pro-inflammatory properties. However, little is known about sCD146 in multiple sclerosis (MS). Here we show that sCD146 is significantly elevated in the cerebrospinal fluid of patients with active MS compared with that of inactive MS or patients with non-demyelinating diseases. Moreover, abnormally increased sCD146 in the CSF of active MS patients correlated with albumin quotient, MBP antibody and MOG antibody from both CSF and sera. Importantly, the level of CSF sCD146 is correlated with levels of inflammatory factors, such as TNF?, IFN?, IL-2, and IL-17A in the CSF. We also found that CSF sCD146 might originate from membrane-bound CD146 on inflamed blood-brain barrier (BBB) endothelial cells. In addition, sCD146 promotes leukocyte transmigration in vitro, at least in part by stimulating the expression of ICAM-1 and VCAM-1 on endothelial cells. Our findings suggest that CSF levels of sCD146 may provide a potential marker for monitoring disease activity in MS patients. PMID:23333866

Duan, H; Luo, Y; Hao, H; Feng, L; Zhang, Y; Lu, D; Xing, S; Feng, J; Yang, D; Song, L; Yan, X



Cerebrospinal fluid biomarkers of neuropathologically diagnosed Parkinson's disease subjects  

PubMed Central

1. Objectives Parkinson's disease (PD) afflicts approximately 1-2% of the population over 50 years of age. No cures or effective modifying treatments exist and clinical diagnosis is currently confounded by a lack of definitive biomarkers. We sought to discover potential biomarkers in the cerebrospinal fluid (CSF) of neuropathologically confirmed PD cases. 2. Methods We compared postmortem ventricular CSF (V-CSF) from PD and normal control (NC) subjects using two-dimensional difference gel electrophoresis (2D-DIGE). Spots exhibiting a 1.5-fold or greater difference in volume between PD patients and controls were excised from the 2D gels, subjected to tryptic digestion and identification of peptides assigned using mass spectrometric/data bank correlation methods. 3. Results Employing this strategy six molecules: fibrinogen, transthyretin, apolipoprotein E, clusterin, apolipoprotein A-1 and glutathione-S-transferase-Pi were found to be different between PD and NC populations. 4: Discussion These molecules have been implicated in PD pathogenesis. Combining biomarker data from multiple laboratories may create a consensus panel of proteins that may serve as a diagnostic tool for this neurodegenerative disorder.

Maarouf, Chera L.; Beach, Thomas G.; Adler, Charles H.; Shill, Holly A.; Sabbagh, Marwan N.; Wu, Terence; Walker, Douglas G.; Kokjohn, Tyler A.; Roher, Alex E.



Cerebrospinal fluid biomarkers mirror rate of cognitive decline.  


The ability to predict future decline in cognitive systems using the cerebrospinal fluid (CSF) biomarkers 42 amino acid form of amyloid-? (A?42) and total tau (T-tau) is not fully understood. In a clinical sample ranging from cognitively healthy to dementia (n = 326), linear regression models were performed in order to investigate the ability of CSF biomarkers to predict cognitive decline in all cognitive domains from baseline to 2-year follow-up. Gender, age, and years of education were included as covariates. In patients with subjective cognitive impairment, T-tau had a small impact on executive functions (r2 = 0.07). T-tau had a small to moderate influence (r2 = 0.06-0.11) on all cognitive functions with the exception of visuospatial functions in patients with mild cognitive impairment (MCI). In patients with dementia, the impact of T-tau was large (r2 = 0.29) on semantic memory. A?42 had a small effect (r2 = 0.07) on speed and executive functions in MCI. In patients with dementia, A?42 had a moderate influence (r2 = 0.13-0.24) on semantic and verbal working memory/fluency. Our results speak in favor of the notion that CSF biomarkers reflect the rate of cognitive decline across the continuum of cognitive impairment from healthy to dementia. CSF predicted subsequent decline in more cognitive domains among MCI cases, but the impact was most pronounced in patients with dementia. PMID:23313924

Rolstad, Sindre; Berg, Anne Ingeborg; Bjerke, Maria; Johansson, Boo; Zetterberg, Henrik; Wallin, Anders



Primary spontaneous cerebrospinal fluid leaks located at the clivus  

PubMed Central

Transclival meningoceles and primary spontaneous cerebrospinal fluid (CSF) leaks at the clivus are extremely rare lesions and only few of them have been reported in the literature. We report here six cases of transclival primary spontaneous CSF leaks through the clivus. A retrospective case study was performed. We reviewed six cases involving sinonasal CSF leaks located at the clivus treated between 1997 and 2009. Presenting symptoms, duration of symptoms, defect size, site of defect, surgical approach and technique of defect closure, intraoperative complications, postoperative complications, and recurrences are discussed. All CSF leaks were located in the upper central part of the clivus. two of six patients showed signs of increased intracranial pressure (ICP) including arachnoid pits and/or empty sella. For three patients a purely transnasal approach was used with multilayer reconstruction using a nonvascularized graft, and three patients underwent a transnasal transseptal approach with a multilayer reconstruction, with nasoseptal flap. No recurrences of CSF leaks at clivus or other sites were observed to date with a mean follow-up of 10.3 years (range, 3–15 years). Spontaneous CSF rhinorrhea located at the clivus is an extremely rare condition. To date, only eight cases have been described. Here, we report the largest group of six consecutive cases. Irrespective of the used reconstruction technique in all cases a 100% closure rate was achieved. However, identification of increased ICP is an essential aspect and this condition should be treated either medically or surgically.

Kitice, Adriano; Vellutini, Eduardo; Balsalobre, Leonardo; Stamm, Aldo



Antibodies to Schistosoma mansoni in human cerebrospinal fluid.  


Cerebrospinal fluid (CSF) and serum samples from patients suspected of having neuroschistosomiasis (NS) were evaluated by an enzyme-linked immunosorbent assay. Monoclonal antibodies of various immunoglobulin isotypes (IgM, IgA, IgE, total IgG, IgG1, IgG2, IgG3, and IgG4) were used to detect antibodies against Schistosoma mansoni soluble egg antigen (SEA) and soluble worm adult preparation (SWAP). Of the 83 CSF samples tested, 55% were reactive to SEA (26% were reactive only to SEA and 29% to both SEA and SWAP), 34% were reactive to SWAP (5% only to SWAP and 29% to both SEA and SWAP), and 40% were not reactive with any antigen. Cases that tested positive for SWAP in CSF and negative in serum were not found. Samples with high specific IgG antibody titers were selected for immunoglobulin isotype profiling. In the CSF samples, the antibodies against SEA and SWAP were mainly IgM, IgG1, and IgG4, although other immunoglobulins were also detected. Interestingly, nine patients had high levels of IgG1 only in the CSF. These results suggest that there is local synthesis of IgG1, and that this isotype could be an important immunologic marker in the diagnosis of NS. PMID:12685632

Magalhães-Santos, Isis F; Lemaire, Denise C; Andrade-Filho, Antonio S; Queiroz, Aristides C; Carvalho, Otávio M; Carmo, Theomira M A; Siqueira, Isadora C; Andrade, Débora M; Rego, Michely F; Guedes, Ana Paula T; Reis, Mitermayer G



Choroid plexus protects cerebrospinal fluid against toxic metals  

SciTech Connect

Although heavy metal ions are known to be toxic to the central nervous system (CNS), the mechanisms by which the CNS may protect itself from initial challenges of such toxic ions is unknown. The choroid plexus is the principal site of formation of the cerebrospinal fluid (CSF) which bathes the brain. We have determined in rats and rabbits that after intraperitoneal administration of lead, cadmium, mercury, and arsenic compounds, these toxic metal ions accumulated in the lateral choroid plexus at concentrations of Pb, Hg, and As that were 70-, 95-, and 40-fold higher, respectively, than those found in CSF. Cd was not detected in the CSF. In addition, concentrations of these heavy metal ions were found to be many fold greater in the choroid plexus than in the brain or blood. The accumulation of Pb in the choroid plexus was dose-dependent and time-related. When the choroid plexus was preincubated, in vitro, with ouabain (1.5 mM), the uptake of Cd from the CSF side of the choroid plexus was inhibited 57%. Cadmium metallothionein was not found in the choroid plexus. Whereas the concentration of reduced glutathione in the choroid plexus was less than that in the brain cortex, the concentration of cysteine was fourfold greater. The lateral choroid plexus sequesters Pb, Cd, As, and Hg. It appears to be one of the important mechanisms that protects the CSF and the brain from the fluxes of toxic heavy metals in the blood.

Wei, Zheng; Perry, D.F.; Nelson, D.L.; Aposhian, H.V. (Univ. of Arizona, Tucson (United States))



Spontaneous skull base meningoencephaloceles and cerebrospinal fluid fistulas.  


Cerebrospinal fluid (CSF) fistulas are characterized by the egress of CSF from the intracranial cavity through an osteodural disruption between the subarachnoid space and a pneumatized structure within the skull base. Depending on the cause, CSF fistulas are classified as acquired or congenital, and acquired fistulas are further classified as traumatic, nontraumatic, or spontaneous. Spontaneous CSF fistulas are considered to result from a multifactorial process and have been postulated to represent a variant of idiopathic intracranial hypertension. However, an anatomic predisposition involving thinning of the cranial base, such as pneumatization of the sinus walls, must also be present. This process creates areas of structural weakness that act as potential pathways for CSF leaks, which most commonly occur in the ethmoid roof, sphenoid sinus, and temporal bone. Because CSF leaks may be overlooked, a result of their asymptomatic or subtle, intermittent course, a high level of suspicion is crucial in making an early diagnosis. However, CSF fistulas may be well seen at computed tomography (CT), which depicts bone defects, and magnetic resonance cisternography, which reveals the contents of herniated tissue. Knowledge of the location and size of the bone defect and herniated contents is crucial for the selection of surgical approach and grafting material. PMID:23479713

Alonso, Raquel Cano; de la Peña, Mar Jimenez; Caicoya, Anne Gomez; Rodriguez, Manuel Recio; Moreno, Elena Alvarez; de Vega Fernandez, Vicente Martinez


Surgical challenge: endoscopic repair of cerebrospinal fluid leak  

PubMed Central

Background Cerebrospinal fluid leaks (CSF) result from an abnormal communication between the subarachnoid space and the extracranial space. Approximately 90% of CSF leak at the anterior skull base manifests as rhinorrhea and can become life-threatening condition. Endoscopic sinus surgery (ESS) has become a common otolaryngologist procedure. The aim of this article is to consider our experience and to evaluate the outcomes in patients who underwent a purely endoscopic repair of CSF leaks of the anterior skull base. Findings Retrospective chart review was performed of all patients surgically treated for CSF leaks presenting to the Section of Nasal and Sinus Disorders at the Service of ENT–Head and Neck Surgery, University Hospital Complex of Santiago de Compostela (CHUS), between 2004 and 2010. A total of 30 patients who underwent repair CSF leak by ESS. The success rate was 93.4% at the first attempt; only two patients (6.6%) required a second surgical procedure, and none of it was necessary to use a craniotomy for closure. Follow-up periods ranged from 4?months to 6?years. Conclusion Identifying the size, site, and etiology of the CSF leak remains the most important factor in the surgical success. It is generally accepted that the ESS have made procedures minimally invasive, and CSF leak is now one of its well-established indications with low morbidity and high success rate, with one restriction for fistulas of the posterior wall of the frontal sinus should be repaired in conjunction with open techniques.



Neurosurgically related nosocomial Acinetobacter baumannii meningitis: report of two cases and literature review.  


Nosocomial meningitis is an uncommon complication of neurosurgical procedures, although nosocomial Gram-negative bacillary meningitis does occur occasionally in neurosurgical intensive care units (NSICUs). Acinetobacter baumannii is a rare cause of nosocomial meningitis, and is an even rarer cause of meningitis outbreaks in NSICUs. We report two cases of A. baumannii meningitis in an NSICU due to suboptimal aseptic technique in obtaining cerebrospinal fluid (CSF) specimens. After institution of infection control measures, i.e. aseptically collecting CSF specimens from distal external ventricular drain ports, there were no further cases. This report also reviews nosocomial Acinetobacter meningitis in adult neurosurgical patients. PMID:19084290

Krol, V; Hamid, N S; Cunha, B A



Prostatic meningeal carcinomatosis presenting as delirium tremens.  

PubMed Central

We report an unusual case of prostatic carcinomatous meningitis and remind clinicians to maintain a high index of suspicion of meningeal involvement when patients with advanced prostatic cancer present with cerebral symptoms, back pain, or neurologic findings. The diagnosis may require repeated cytologic examinations of cerebrospinal fluid, and immunocytochemical stains should be considered to confirm a prostatic source if malignant cells are identified. Androgen ablative therapy may give prolonged remissions, especially in patients with previously untreated tumours. Images Figure 1 Figure 2

Rubins, J. B.; Guzman-Paz, M. J.



Reduction of Cerebrospinal Fluid Pressure by Hypocapnia: Changes in Cerebral Blood Volume, Cerebrospinal Fluid Volume, and Brain Tissue Water and Electrolytes  

Microsoft Academic Search

Summary: The study examined the role of cerebral blood volume (CBV), cerebrospinal fluid (CSF) volume, and brain tissue water and electrolytes on CSF pressure during 4 h of hypocapnia in dogs. Group I (n = 6) was examined during hypocapnia (Paco2 20 mm Hg), with no intracranial mass being present. Group II (n = 6) was examined with an intracranial

Alan A. Artru



Cerebrospinal Fluid Biomarkers for Parkinson Disease Diagnosis and Progression  

PubMed Central

Background There is a clear need to develop biomarkers for Parkinson disease (PD) diagnosis, differential diagnosis of parkinsonian disorders, and monitoring disease progression. We and others have demonstrated that a decrease in DJ-1 and/or ?-synuclein in the cerebrospinal fluid (CSF) is a potential index for PD diagnosis, but not for PD severity. Methods Using highly sensitive and quantitative Luminex assays, we measured total tau, phosphorylated tau, amyloid beta peptide 1-42 (A?1-42), Flt3 ligand and fractalkine levels in CSF in a large cohort of PD patients at different stages as well as healthy and diseased controls. The utility of these five markers was evaluated for disease diagnosis and severity/progression correlation alone, as well as in combination with DJ-1 and ?-synuclein. The major results were further validated in an independent cohort of cross-sectional PD patients as well as in PD cases with CSF samples collected longitudinally. Findings The results demonstrated that combinations of these biomarkers could differentiate PD patients not only from normal controls but also from patients with Alzheimer disease and multiple system atrophy. Particularly, with CSF Flt3 ligand, PD could be clearly differentiated from multiple system atrophy, a disease that overlaps with PD clinically, with excellent sensitivity (99%) and specificity (95%). In addition, we identified CSF fractalkine/A?1-42 that positively correlated with PD severity in cross-sectional samples as well as with PD progression in longitudinal samples. Interpretation We have demonstrated that this panel of seven CSF proteins could aid in PD diagnosis, differential diagnosis, and correlation with disease severity and progression.

Shi, Min; Bradner, Joshua; Hancock, Aneeka M.; Chung, Kathryn A.; Quinn, Joseph F.; Peskind, Elaine R.; Galasko, Douglas; Jankovic, Joseph; Zabetian, Cyrus P.; Kim, Hojoong M.; Leverenz, James B.; Montine, Thomas J.; Ginghina, Carmen; Kang, Un Jung; Cain, Kevin C.; Wang, Yu; Aasly, Jan; Goldstein, David S.; Zhang, Jing



Serum and cerebrospinal fluid cytokine concentrations in subacute sclerosing panencephalitis.  


Subacute sclerosing panencephalitis (SSPE) is a neurodegenerative disease due to persistent measles virus infection. Its immunopathogenesis is unknown. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-6, IL-10 and IL-4 concentrations were measured in cerebrospinal fluid (CSF) and serum samples from 30 SSPE patients and 19 control subjects by cytometric bead array. CSF and serum IFN-gamma, IL-12 and IL-18 levels were measured in 18 SSPE patients by ELISA. Serum IL-4 and IL-10 (p<0.001), CSF IL-4 (p<0.001) and IL-6 (p=0.049) concentrations were lower, and serum IL-2 concentrations, higher (p=0.001) in SSPE patients. Serum TNF-alpha and IL-6, CSF TNF-alpha, IL-10, and IL-2 concentrations were not different between SSPE and control groups. Serum IFN-gamma levels were higher in stage I and II than stage III patients (p<0.05), whereas there was no difference between stages in terms of other cytokines. The levels of Th2-type cytokines: IL-4, IL-6 and IL-10 were suppressed in our SSPE cases. This finding, along with relatively elevated IFN-gamma and IL-2 levels, may suggest more active effector T cells compared to regulatory T cells (Treg), especially induced Treg, in early disease. High serum IL-2 concentrations might indicate peripheral Th1 activation. Discrepancies between various reports in the literature should be examined in view of the ages, stage and treatments of the patients studied. The interplay of various cytokines or cellular systems which may vary over time and between patients. Studies of treatment measures favoring the preservation of the early inflammatory response may be of interest in SSPE. PMID:19481385

Aydin, Omer Faruk; Ichiyama, Takashi; Anlar, Banu



Characterization of Acid Sphingomyelinase Activity in Human Cerebrospinal Fluid  

PubMed Central

Background As a key enzyme in sphingolipid metabolism, acid sphingomyelinase (ASM) is involved in the regulation of cell fate and signaling via hydrolysis of sphingomyelin to form ceramide. While increased activity of the lysosomal form has been associated with various pathological conditions, there are few studies on secretory ASM limited only to cell models, plasma or serum. Methods An optimized assay based on a fluorescent substrate was applied to measure the ASM activity in cerebrospinal fluid (CSF) collected from mice and from 42 patients who were classified as controls based on normal routine CSF values. Results We have detected ASM activity in human CSF, established a sensitive quantitative assay and characterized the enzyme’s properties. The enzyme resembles plasmatic ASM including protein stability and Zn2+-dependence but the assays differ considerably in the optimal detergent concentration. Significantly increased activities in the CSF of ASM transgenic mice and undetectable levels in ASM knock-out mice prove that the measured ASM activity originates from the ASM-encoding gene SMPD1. CSF localized ASM activities were comparable to corresponding serum ASM levels at their respective optimal reaction conditions, but no correlation was observed. The large variance in ASM activity was independent of sex, age or analyzed routine CSF parameters. Conclusions Human and mouse CSF contain detectable levels of secretory ASM, which are unrelated to serum ASM activities. Further investigations in humans and in animal models will help to elucidate the role of this enzyme in human disease and to assess its value as a potential biomarker for disease type, severity, progress or therapeutic success.

Muhle, Christiane; Huttner, Hagen B.; Walter, Silke; Reichel, Martin; Canneva, Fabio; Lewczuk, Piotr; Gulbins, Erich; Kornhuber, Johannes



Cerebrospinal Fluid Biomarkers, Education, Brain Volume and Future Cognition  

PubMed Central

Objective To evaluate the combination of cerebrospinal fluid biomarkers of A?42, tau, and phosphorylated tau (ptau181) with education and normalized whole brain volume (nWBV) to predict incident cognitive impairment and test the cognitive/brain reserve hypothesis. Design Longitudinal cohort study. Setting Charles F. and Joanne Knight Alzheimer’s Disease Research Center of Washington University, St. Louis, Missouri. Participants Convenience sample of 197 participants aged 50 years and above, with normal cognition (Clinical Dementia Rating [CDR] of 0) at baseline, followed for a mean of 3.3 years. Main outcome measure Time to cognitive impairment (CDR ? 0.5). Results Three-factor interactions between the baseline biomarker values, education, and nWBV were found for Cox proportional hazards models testing tau (p=.03) and ptau (p=.008). Among those with lower tau values, nWBV (hazard ratio [HR]=.54, 95% confidence interval [CI]=.31–.91; p=.02), but not education, was related to time to cognitive impairment. For participants with higher tau values, education interacted with nWBV to predict incident impairment (p=.01). For individuals with lower ptau values, there was no effect of education or nWBV. Education interacted with nWBV to predict incident cognitive impairment among those with higher ptau values (p=.02). In models testing A?42, larger nWBV was associated with a slower time to cognitive impairment (HR=.84, 95%CI=.71–.99, p=.0348), but there was no effect of A?42 or education. Conclusions Among individuals with higher levels of CSF tau and ptau, but normal cognition at baseline, time to incident cognitive impairment is moderated by education and brain volume as predicted by the cognitive/brain reserve hypothesis.

Roe, Catherine M.; Fagan, Anne M.; Grant, Elizabeth A.; Marcus, Daniel S.; Benzinger, Tammie L. S.; Mintun, Mark A.; Holtzman, David. M.; Morris, John C.



Thrombin and its precursor in human cerebrospinal fluid.  


The blood coagulation cascade proteolytic enzyme, thrombin, affects many cell types, including neurons and astrocytes, in which it prevents process outgrowth and induces significant morphological degeneration and even cell death. Since thrombin may contribute significantly to pathological conditions in the central nervous system (CNS), where it is synthesized locally, we measured the levels of thrombin and its precursor, prothrombin, in the cerebrospinal fluid (CSF) of 67 individuals from 6 groups: non-neurologic controls (NNC); spinal degenerative disease (SDD); peripheral nerve disease (PND); cerebrovascular, neuroimmune and seizure disorders and tumor (CNSD); traumatic brain injury (TBI) and neurodegenerative disorders (NDD). We employed a sensitive chromogenic assay utilizing the thrombin specific tripeptide substrate, S-2238, to evaluate CSF levels of thrombin and prothrombin. The latter estimated after its conversion to active enzyme by the snake venom prothrombinase, ecarin. No measurable active thrombin was detected in these CSF samples. However, activatable prothrombin was measured in all groups. The mean activatable prothrombin concentrations (in nM) were 7.26 +/- 3.39 (NNC); 8.85 +/- 3.09 (SDD); 6.78 +/- 2.58 (PND); 6.33 +/- 3.87 (CNSD); 5.10 +/- 1.86 (TBI), and 7.80 +/- 3.27 (NDD). Duncan's multiple comparison test showed significant reduction (p <0.05) in prothrombin levels of the TBI group. Our data suggests that the prothrombin zymogen gains access to the CSF, likely across either an intact or compromised blood-brain barrier (BBB), in increased amounts with age. Reduced levels in TBI patients may have diagnostic and/or prognostic value. PMID:9423797

Smirnova, I V; Salazar, A; Arnold, P M; Glatt, S; Handler, M; Festoff, B W



Diagnostic accuracy of urinary reagent strip to determine cerebrospinal fluid chemistry and cellularity  

PubMed Central

Background: The gold standard for diagnosis of meningitis depends on cerebrospinal fluid (CSF) examination by microscopy, biochemistry, and culture, which require an experienced microscopist and laboratory support. We conducted this study to determine if urinary reagent strip is useful to make a semi-quantitative assessment of protein, glucose, and presence of leukocyte esterase in CSF. Materials and Methods: All consecutive CSF samples were evaluated in a blinded fashion. CSF was tested using Combur-10 urinary reagent strip as an index test, and CSF microscopy and biochemistry as reference standards. Combur-10 (Boehringer Mannheim) is a urinary reagent strip used to estimate ten parameters including protein, glucose, and leukocytes. We estimated diagnostic accuracy of each index test using corresponding cut-off levels (glucose 1 + vs. CSF glucose >50 mg/dL; protein 1 + and 2 + vs. CSF protein >30 mg/dL and >100 mg/dL; leukocyte esterase positivity vs. >10 granulocytes in CSF sample). We constructed receiver operating curves (ROC) to evaluate overall performance of index tests and estimated area under the curve (AUC). Results: CSF samples of 75 patients were included in the study. All the three indicator tests (CSF cells, protein, and glucose) were normal in 17 (22.6%) samples. Of the three tests, diagnostic accuracy of protein estimation (1 + or more on reagent strip) was best for detection of CSF proteins greater than 30 mg/dL [sensitivity 98.1% (95% CI 90.1-100%); specificity 57.1% (95% CI 34-78.2%)], with AUC of 0.97. Sensitivity and specificity for 2 + on reagent strip and CSF protein > 100 mg/dL were 92.6% (95% CI 75.1-99.1) and 87.5% (95% CI 74.8-95.3), respectively, with AUC of 0.96 (95% CI 0.92-1.01). Leukocyte esterase positivity by test strip had a sensitivity of 85.2 (95% CI 66.3-95.8%) and specificity of 89.6 (95% CI 77.3-96.5%) for detection of CSF granulocytes of more than 10/mm3. Conclusion: Existing urinary reagent strips can be used to diagnose meningitis in low-resource settings.

Joshi, Deepti; Kundana, Keerthi; Puranik, Apurva; Joshi, Rajnish



Meningitis-Retention Syndrome as a Presentation of West Nile Virus Meningitis  

PubMed Central

A 26-year-old previously healthy man presented with fever, urinary retention, nuchal rigidity, and hyperreflexia but with a clear sensorium. His initial spinal fluid results were consistent with aseptic meningitis from West Nile virus infection, and this was confirmed by serological studies on blood and cerebrospinal fluid. Computed tomography and magnetic resonance imaging studies were unremarkable. He received supportive care and urinary catheterization to prevent bladder injury from overdistension. He was discharged home without recurrence of urinary retention after five days of hospitalization. Therefore, this case report describes the first case of West Nile virus meningitis in a patient with the meningitis-retention syndrome.

Laengvejkal, Pavis; Argueta, Erwin; Limsuwat, Chok; Nugent, Kenneth



New Guinea Pig Model of Cryptococcal Meningitis?  

PubMed Central

We developed a guinea pig model of cryptococcal meningitis to evaluate antifungal agents. Immunosuppressed animals challenged intracranially with Cryptococcus neoformans responded to fluconazole and voriconazole. Disease was monitored by serial cerebrospinal fluid (CSF) cultures and quantitative organ cultures. Our model produces disseminating central nervous system disease and responds to antifungal therapy.

Kirkpatrick, William R.; Najvar, Laura K.; Bocanegra, Rosie; Patterson, Thomas F.; Graybill, John R.



Combination antifungal therapies for HIV-associated cryptococcal meningitis: a randomised trial  

Microsoft Academic Search

BACKGROUND: It frequently takes more than 2 weeks for drug treatments for cryptococcal meningitis to sterilise cerebrospinal fluid (CSF). In-vitro and animal studies lend support to the use of combinations of amphotericin B, flucytosine, and fluconazole for treatment of cryptococcosis. We compared the fungicidal activity of combinations of these drugs for initial treatment of patients with cryptococcal meningitis. METHODS: 64

Annemarie E Brouwer; Adul Rajanuwong; Wirongrong Chierakul; George E Griffin; Robert A Larsen; Nicholas J White; Thomas S Harrison



Características clínico-microbiológicas de la meningitis por Streptococcus pneumoniae resistente a la penicilina  

Microsoft Academic Search

Objective. To evaluate the susceptibility to antibiotics of Streptococcus pneumoniae isolated from cerebrospinal fluid of children with meningitis. To describe and compare the clinical and microbiological characteristics, treatment and outcome among children infected with strains either suscep- tible or resistant to penicillin and cephalosporin. Material and methods. A total of 38 children with pneumococcal meningitis were prospectively enrolled in the

Demóstenes Gómez-Barreto; Ernesto Calderón-Jaimes; Romeo S. Rodríguez; Luz Elena Espinosa de los Monteros; Maricruz Juárez



Ultrasensitive Stain for Proteins in Polyacrylamide Gels Shows Regional Variation in Cerebrospinal Fluid Proteins  

NASA Astrophysics Data System (ADS)

A new silver stain for electrophoretically separated polypeptides can be rapidly and easily used and can detect as little as 0.01 nanogram of protein per square millimeter. When employed with two-dimensional electrophoresis, it should permit qualitative and quantitative characterization of protein distributions in body fluids and tissues. It has been used to demonstrate regional variations in cerebrospinal fluid proteins.

Merril, Carl R.; Goldman, David; Sedman, Sylvia A.; Ebert, Michael H.



Prostaglandin D Synthase Concentration in Cerebrospinal Fluid and Serum of Patients with Neurological Disorders  

Microsoft Academic Search

Prostaglandin D synthase (PGD synthase) or ?-trace protein is a major constituent of human cerebrospinal fluid (CSF) representing ?3% of the total CSF protein. We have recently developed a highly specific immunofluorometric assay for PGD synthase, which enabled us to quantify the presence of PGD synthase in fluids and tissues not associated with the CNS. In this report we provide

Dimitrios N Melegos; Mark S Freedman; Eleftherios P Diamandis



Mammalian embryonic cerebrospinal fluid proteome has greater apolipoprotein and enzyme pattern complexity than the avian proteome.  


During early stages of embryo development, the brain cavity is filled with Embryonic Cerebro-Spinal Fluid, which has an essential role in the survival, proliferation and neurogenesis of the neuroectodermal stem cells. We identified and analyzed the proteome of Embryonic Cerebro-Spinal Fluid from rat embryos (Rattus norvegicus), which includes proteins involved in the regulation of Central Nervous System development. The comparison between mammalian and avian Embryonic Cerebro-Spinal Fluid proteomes reveals great similarity, but also greater complexity in some protein groups. The pattern of apolipoproteins and enzymes in CSF is more complex in the mammals than in birds. This difference may underlie the greater neural complexity and synaptic plasticity found in mammals. Fourteen Embryonic Cerebro-Spinal Fluid gene products were previously identified in adult human Cerebro-Spinal Fluid proteome, and interestingly they are altered in patients with neurodegenerative diseases and/or neurological disorders. Understanding these molecules and the mechanisms they control during embryonic neurogenesis may contribute to our understanding of Central Nervous System development and evolution, and these human diseases. PMID:16335996

Parada, Carolina; Gato, Angel; Bueno, David


Neurogranin in cerebrospinal fluid as a marker of synaptic degeneration in Alzheimer's disease.  


Synaptic pathology occurs early in Alzheimer's disease (AD) development, and cerebrospinal fluid biomarkers for synaptic damage may be altered early in the disease process. In the present study we examined cerebrospinal fluid levels of the postsynaptic protein neurogranin in patients with mild cognitive impairment (MCI) or AD and controls. The low neurogranin level in cerebrospinal fluid required enrichment by immunoprecipitation prior to mass spectrometric identification and semi-quantitative immunoblot analysis. Relative quantification revealed a significant increase of neurogranin in the AD group compared with controls, while the MCI group was not statistically different from either controls or the AD group. The concentrations of the AD biomarkers T-tau, P-tau(181) and A?(42) were significantly changed in the control and MCI groups compared with the AD group, but no significant differences were found between the MCI group and controls for the three biomarkers. Nevertheless, a trend towards increasing levels of neurogranin, T-tau and P-tau(181) was found in cerebrospinal fluid from MCI patients compared with controls. The elevated neurogranin levels in the MCI and AD groups might reflect synaptic degeneration. These results together suggest that cerebrospinal fluid neurogranin might be valuable together with the established AD biomarkers in the early diagnosis of AD and warrants further studies to determine the diagnostic value of neurogranin. PMID:20875798

Thorsell, Annika; Bjerke, Maria; Gobom, Johan; Brunhage, Eva; Vanmechelen, Eugeen; Andreasen, Niels; Hansson, Oskar; Minthon, Lennart; Zetterberg, Henrik; Blennow, Kaj



Oligoclonal immunoglobulins in cerebrospinal fluid during varicella zoster virus (VZV) vasculopathy are directed against VZV.  


Limited analyses of cerebrospinal fluid from patients with central nervous system infections have shown that the oligoclonal IgG is antibody directed against the agent that causes disease. Using a new method involving binding of IgG to beads coated with lysates prepared from candidate infectious antigens, we showed that the oligoclonal IgG in cerebrospinal fluid of a patient with chronic varicella zoster virus vasculopathy is directed against the causative virus. This approach holds promise in identifying and purifying the relevant oligoclonal IgGs in inflammatory central nervous system diseases of unknown cause. PMID:14520657

Burgoon, Mark P; Hammack, Barbara N; Owens, Gregory P; Maybach, Amy L; Eikelenboom, M Judith; Gilden, Donald H



Oligoclonal Immunoglobulins in Cerebrospinal Fluid during Varicella Zoster Virus (VZV) Vasculopathy Are Directed against VZV  

PubMed Central

Limited analyses of cerebrospinal fluid from patients with central nervous system infections have shown that the oligoclonal IgG is antibody directed against the agent that causes disease. Using a new method involving binding of IgG to beads coated with lysates prepared from candidate infectious antigens, we showed that the oligoclonal IgG in cerebro-spinal fluid of a patient with chronic varicella zoster virus vasculopathy is directed against the causative virus. This approach holds promise in identifying and purifying the relevant oligoclonal IgGs in inflammatory central nervous system diseases of unknown cause.

Burgoon, Mark P.; Hammack, Barbara N.; Owens, Gregory P.; Maybach, Amy L.; Judith Eikelenboom, M.; Gilden, Donald H.



Effects of negatively charged aerosol on blood and cerebrospinal fluid parameters in rats  

NASA Astrophysics Data System (ADS)

Adult male rats were exposed for 90 to 140 minutes to negatively charged tapwater aerosol. Blood and cerebrospinal fluid samples were collected to determine effects of the exposure on selected hematologic and serum chemistry parameters, and ionized calcium and pH in cerebrospinal fluid. Of the 27 variables assayed, 24 yielded sufficient data for statistical analysis. Two parameters, serum alkaline phosphatase and mean corpuscular hemoglobin concentration, were significantly different (p<0.05) from control values, probably representing chance occurrences. It appears that whatever biological effects may be exerted by electro-aerosols, they are not mediated by the parameters investigated in this study.

Wehner, A. P.; Ragan, H. A.; Jaffe, R. A.; Weigel, R. J.; Lundstrom, D. L.



Insulin-like growth factor system in serum and cerebrospinal fluid in patients with multiple sclerosis.  


The insulin-like growth factor (IGF) system influences oligodendrocyte survival, myelination, and immune functions. We examined whether alterations in the circulating IGF system occur in multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system. We measured concentrations of IGF-I, IGF-II, and insulin-like growth factor binding proteins -1, -2, and -3 in both serum and cerebrospinal fluid from MS patients and age- and sex-matched controls. IGFBP-1 was not detectable in cerebrospinal fluid. We found no significant differences in any of the other components between patients with MS and controls. PMID:9870347

Wilczak, N; Schaaf, M; Bredewold, R; Streefland, C; Teelken, A; De Keyser, J



Pneumocephalus Associated with Cerebrospinal Fluid Fistula as a Complication of Spinal Surgery: A Case Report  

PubMed Central

Pneumocephalus is a well-known condition following head trauma, but is rare as an injury or as a result of surgery of the spine. We present a 76-year-old patient with a rare case of pneumocephalus associated with a cerebrospinal fluid fistula as a complication of surgical treatment for cervical myelopathy. Although cerebrospinal fluid leakage was noted and the injured dura was carefully sutured at operation, tension pneumocephalus occurred. The resultant pneumocephalus was diagnosed based on neurogenic symptoms including sudden convulsion, head radiograph, and computed tomography scan. The benign course of the pneumocephalus postdiagnosis did not require secondary operation.

Sasaki, Ken; Matsumoto, Tomoyuki; Mizuno, Toshiyuki; Ikuta, Shinichi; Akisue, Toshihiro; Fujioka, Hiroyuki; Doita, Minoru; Kurosaka, Masahiro; Kuroda, Ryosuke



Klebsiella meningitis in Taiwan: an overview.  


Klebsiella infection has been considered to be an uncommon cause of meningitis. To determine its incidence and clinical features, we reviewed the microbiologic records of cerebrospinal fluid (CSF) and blood cultures and the medical records of patients with bacterial meningitis admitted between 1981 and 1995. Klebsiella meningitis was diagnosed in 79 patients with 83 episodes. All patients had klebsiella isolated from CSF and/or blood and typical symptoms and signs of acute bacterial meningitis. Of these, 74 were over 16 years of age and 2 of the 5 children were infants. There was an increased prevalence rate of klebsiella meningitis after 1986. Of the 83 episodes, only 9 occurred between 1981 and 1986, accounting for 7.8% of 115 cases with CSF and/or blood culture-proven acute bacterial meningitis, whereas in 1987-95, there were 74 episodes accounting for 17.7% of 419 bacteriologically proven cases. K. pneumoniae accounted for 69 episodes, K. oxytoca, 11 episodes and K. ozaenae, 3 episodes. Male gender, diabetes mellitus and liver cirrhosis were commonly associated with K. pneumoniae meningitis. Neurosurgical procedures were frequently associated with K. oxytoca meningitis. All three patients with K. ozaenae meningitis had a primary disease of the nasopharyngeal pathway. The mortality rate due to K. pneumoniae was 48.5%, K. oxytoca, 10% and K. ozaenae, 0%. In patients with K. pneumoniae meningitis, poor prognostic factors included age over 60 years, diabetes mellitus, bacteremia and severe neurological deficits on the first day of treatment. PMID:9363011

Tang, L M; Chen, S T; Hsu, W C; Chen, C M



Steroid Hormones and Steroid Hormone Binding Globulins in Cerebrospinal Fluid Studied in Individuals with Intact and with Disturbed Blood-Cerebrospinal Fluid Barrier  

Microsoft Academic Search

We measured in simultaneously withdrawn cerebrospinal fluid (CSF) and serum samples from 56 endocrinologically grossly normal patients the concentrations of several lipophilic unconjugated steroids [i.e. dehydroepiandrosterone (DHEA), androstenedione, cortisol, progesterone, testosterone] and their hydrophilic counterparts, i.e. DHEA-sulfate, or hydrophilic binding proteins, i.e. albumin, sex hormone-binding globulin (SHBG) and corticosterone-binding globulin (CBG). CSF levels of total (i.e. free plus protein-bound) DHEA,

Siegfried Schwarz; Peter Pohl



Selenium speciation in paired serum and cerebrospinal fluid samples.  


Se speciation was performed in 24 individual paired serum and cerebrospinal fluid (CSF) samples from neurologically healthy persons. Strong anion exchange (SAX) separation, coupled to inductively coupled plasma-dynamic reaction cell-mass spectrometry (ICP-DRC-MS), was employed. Species identification was done by standard matched retention time, standard addition and by size exclusion chromatography followed from SAX (2-D SEC-SAX-ICP-DRC-MS) and by SAX followed from CE-ICP-DRC-MS (2-D SAX-CE-ICP-DRC-MS). Limit of detection (LoD, 3×standard deviation (SD) of noise) was in the range of 0.026-0.031 ?g/L for all investigated species and thus was set uniformly to 0.032 ?g/L. Quality control for total Se determination was performed by analysing control materials "human serum" and "urine", where determined values met target values. Several Se species were found in both sample types having following median values (sequence: serum/CSF, each in ?g Se/L): total Se, 58.39/0.86; selenoprotein P (SePP), 5.19/0.47; Se-methionine (SeM), 0.23/?65 ?g/L; however, SePP(-CSF) appeared independent of SePP(-serum). For Se-HSA(-serum) versus (vs.) Se-HSA(-CSF), a weak linear relationship was found (r(2)=0.1722). On the contrary, for anti-oxidative Se-enzymes, higher r (2) values were calculated: GPx(-serum) vs. GPx(-CSF), r(2)=0.3837; TrxR(-serum) vs. TrxR(-CSF), r(2)=0.6293. Q(-Se-species) values (= ratios of CSF(-Se-species)/serum(-Se-species)) were compared with the Q (-Alb) value (HSA(-CSF)/HSA(-serum)=clinical index of NB integrity) for deeper information about NB passage of Se species. The Q (-Se-HSA) value (3.8×10(-3)) was in accordance to the molecular mass dependent restriction at NB (Q(-Alb) at 5.25×10(-3)). Increased Q values were seen for TrxR (21.3×10(-3)) and GPx (8.3×10(-3)) which are not (completely) explained by molecular size. For these two anti-oxidative Se-enzymes (GPx, TrxR), we hypothesize that there might be either a facilitated diffusion across NB or they might be additionally synthesized in the brain. PMID:22868477

Solovyev, Nikolay; Berthele, Achim; Michalke, Bernhard



Tau, Phospho-Tau, and S-100B in the Cerebrospinal Fluid of Children With Multiple Sclerosis  

Microsoft Academic Search

Axonal injury and glial activation are an early neuropathologic event in adults with multiple sclerosis. To investigate whether markers of axonal injury and glial activation are already elevated in the cerebrospinal fluid of children with multiple sclerosis, we studied the cerebrospinal fluid of 25 children with multiple sclerosis and 67 controls for the presence of tau, phospho-tau, and S-100B proteins

Kevin Rostasy; Esther Withut; Daniela Pohl; Peter Lange; Barbara Ciesielcyk; Ricarda Diem; Jutta Gärtner; Markus Otto



Mollaret meningitis: case report with a familial association.  


Mollaret meningitis is a syndrome characterized by recurrent bouts of meningitis that occur over a period of several years in an affected patient. Also known as recurrent lymphocytic meningitis, this entity involves repeated episodes of headache, stiff neck, fever, and cerebrospinal fluid pleocytosis. Herpes simplex virus type 2 is the most frequently implicated causative agent, and treatment involves the use of antiviral medications. We describe a case of Mollaret meningitis in a 47-year-old man who presented to the emergency department with his eighth episode of meningitis during a period of 20 years. Cerebrospinal fluid polymerase chain reaction testing for herpes simplex virus type 2 was positive, and further testing excluded other common viral, bacterial, and inflammatory causes of meningeal irritation. The patient's family history was significant for a brother who also had multiple episodes of aseptic meningitis during a period of several years. This represents the first published report of a possible familial association involving Mollaret meningitis. It is likely that Mollaret meningitis is underrecognized among emergency physicians, and improved recognition of this entity may limit unwarranted antibiotic use and shorten or eliminate unnecessary hospital admission. PMID:20825883

Jones, Christopher W; Snyder, Graham E



Drug-resistant tuberculous meningitis.  


Drug-resistant tuberculosis, including drug-resistant tuberculous meningitis, is an emerging health problem in many countries. An association with Beijing strains and drug resistance-related mutations, such as mutations in katG and rpoB genes, has been found. The pathology, clinical features and neuroimaging characteristics of drug-resistant tuberculous meningitis are similar to drug-responsive tuberculous meningitis. Detection of mycobacteria in cerebrospinal fluid (CSF) by conventional methods (smear examination or culture) is often difficult. Nucleic acid amplification assays are better methods owing to their rapidity and high sensitivity. The Xpert MTB/RIF assay (Cepheid, CA, USA) is a fully-automated test that has also been found to be effective for CSF samples. Treatment of multidrug-resistant tuberculous meningitis depends on the drug susceptibility pattern of the isolate and/or the previous treatment history of the patient. Second-line drugs with good penetration of the CSF should be preferred. Isoniazid monoresistant disease requires addition of another drug with better CSF penetration. Drug-resistant tuberculous meningitis is associated with a high mortality. HIV infected patients with drug-resistant tuberculous meningitis have severe clinical manifestations with exceptionally high mortality. Prevention of tuberculosis is the key to reduce drug-resistant tuberculous meningitis. PMID:23750732

Garg, Ravindra K; Jain, Amita; Malhotra, Hardeep S; Agrawal, Avinash; Garg, Rajiv



Seizures and retrograde amnesia with cerebrospinal fluid changes following H1N1 influenza vaccination.  


Vaccination against H1N1 influenza of healthcare workers of has been a standard measure to control the epidemic in many countries. Most side effects are minor and transient. Guillain Barre Syndrome and optic neuritis have been major concerns. We report a case of seizures with retrograde amnesia associated with cerebrospinal fluid changes following the H1N1 vaccine. PMID:21840464

Mitrakrishnan, Shivanthan; Ranjanie, Gamage; Thirunavakarasu, Thivakaran; Manjula, Caldera; Nayananjani, Karunasena



Adiponectin and Resistin in Human Cerebrospinal Fluid and Expression of Adiponectin Receptors in the Human Hypothalamus  

Microsoft Academic Search

Context: The adipokine leptin has critical importance in central appetite regulation. In contrast to some suggestion of adiponectin influencing energy homeostasis in rodents, there is no evidence for adiponectin or resistin entering the human blood-brain barrier. Objective: The objective was to establish the presence of adiponectin or resistin in human cerebrospinal fluid (CSF) and to compare their distribution with leptin.

Katarina Kos; Alison L. Harte; Nancy F. da Silva; Anton Tonchev; Georgi Chaldakov; Sean James; David R. Snead; Barbara Hoggart; Joseph P. O'Hare; Philip G. McTernan; Sudhesh Kumar


Proposal of “evolution theory in cerebrospinal fluid dynamics” and minor pathway hydrocephalus in developing immature brain  

Microsoft Academic Search

Background  The specificity of cerebrospinal fluid (CSF) dynamics in the immature brain still remains unknown. In our data previously published, the transependymal intraparenchymal CSF pathway (the minor pathway) plays a significant role in various degrees in the alternative CSF passage. Now, there is a growing consensus in the age differences in the outcome of neuroendoscopic ventriculostomy in treatment of non-communicating types

Shizuo Oi; Concezio Di Rocco



Serial cerebrospinal fluid sampling in a rat model to study drug uptake from the nasal cavity  

Microsoft Academic Search

Drug transport from the nasal cavity to the brain has gained much interest in the last decade. In the present study, a model was developed to determine the uptake of drugs into the cerebrospinal fluid (CSF) after nasal delivery in rats. CSF samples were taken using a cisternal puncture method. In this method, a needle is advanced through the skin

Mascha P van den Berg; Stefan G Romeijn; J. Coos Verhoef; Frans W. H. M Merkus



Chromogranin A in Cerebrospinal Fluid: A Biochemical Marker for Synaptic Degeneration in Alzheimer’s Disease?  

Microsoft Academic Search

Biochemical markers for AD would be of great value both to improve the clinical diagnostic accuracy in scientific studies and to increase the knowledge of the pathogenesis of the disorder. One of the main features of AD is a degeneration of synapses. Therefore, we examined if chromogranin A (CrA), the major protein of large dense-core synaptic vesicles, in cerebrospinal fluid

K. Blennow; P. Davidsson; A. Wallin; R. Ekman



Tetranectin is a potential biomarker in cerebrospinal fluid and serum of patients with epilepsy  

Microsoft Academic Search

BackgroundTetranectin (TN) is a plasminogen kringle 4 binding protein and regulates fibrinolysis and proteolytic processes via binding to plasminogen. A previous proteomics study identified TN in the cerebrospinal fluid (CSF) of epileptic patients but not in healthy controls. We determined the concentrations of TN in CSF and serum of epileptic patients to evaluate the changes in TN levels after epileptic

Liang Wang; Yumin Pan; Dan Chen; Zheng Xiao; Zhiqin Xi; Fei Xiao; Xuefeng Wang



Metal Concentrations in Plasma and Cerebrospinal Fluid in Patients with Alzheimer’s Disease  

Microsoft Academic Search

Background\\/Aims: The homeostasis of essential metals such as copper, iron, selenium and zinc may be altered in the brain of subjects with Alzheimer’s disease (AD). Methods: Concentrations of metals (magnesium, calcium, vanadium, manganese, iron, cobalt, nickel, copper, zinc, selenium, rubidium, strontium, molybdenum, cadmium, tin, antimony, cesium, mercury and lead) were determined in plasma and cerebrospinal fluid (CSF) by inductively coupled

Lars Gerhardsson; Thomas Lundh; Lennart Minthon; Elisabet Londos



Cerebrospinal fluid leak associated with nasal continuous positive airway pressure treatment for obstructive sleep apnoea  

Microsoft Academic Search

Clear rhinorrhoea is a common symptom in patients with obstructive sleep apnoea (OSA), which may worsen with nasal continuous positive airway pressure treatment (nCPAP). However, rhinorrhoea can also be the presenting symptom of cerebrospinal fluid (CSF) leak, which is due to a communication between the subarachnoid space and the nasal cavity or sinuses. We report another case of a patient

Jean Yared; Jaafar El Annan



Excitatory Amino Acids in Cerebrospinal Fluid of Patients with Acute Head Injuries  

Microsoft Academic Search

Background: The excitatory amino acids (EAAs) gluta- mate (Glu) and aspartate (Asp) play a role in the pathogenesis of postischemic and posttraumatic brain insult. The changes of EAAs in cerebrospinal fluid (CSF) of patients with traumatic brain injury are incom- pletely understood. Methods: We used reversed-phase HPLC with precol- umn derivatization with o-phthalaldehyde and fluores- cence detection to measure Glu

Zhang Hong; Zhang Xinding; Zhang Tianlin; Chen Liren


Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer's disease patients  

Microsoft Academic Search

A new sandwich ELISA is described which shows specificity for tau phosphorylated at threonine 231 and preferentially reacts with Alzheimer's disease (AD) brain extracts relative to other dementias. This assay was used to analyze 58 antemortem cerebrospinal fluid samples. Twenty-three of 27 AD samples (85% sensitivity) yielded signals greater than the cutoff, while only one of 31 non-AD samples (97%

Russell Kohnken; Katharina Buerger; Raymond Zinkowski; Caudill Miller; Daniel Kerkman; John DeBernardis; Jifang Shen; Hans-Jürgen Möller; Peter Davies; Harald Hampel



Cystatin C in cerebrospinal fluid is not a diagnostic test for pain in humans  

Microsoft Academic Search

A recent subtractive cDNA cloning study in rats demonstrated an unexpected increase in expression of the proteinase inhibitor, cystatin C in the spinal cord during acute peripheral inflammation, suggesting this protein may be involved in the pathogenesis of persistent pain. A subsequent study of 10 women suggested that prolonged labor pain resulted in increased cystatin C concentrations in cerebrospinal fluid,

James C Eisenach; John A Thomas; Richard L Rauck; Regina Curry; Xinhui Li



Desmoid tumor arising around the distal tubing of a cerebrospinal fluid shunt.  


A case of desmoid tumor in the abdominal wall as a cause of malfunction of a cerebrospinal fluid shunt is presented. The desmoid tumor arose from the reactive fibrose tissue formed around the silastic distal tubing and caused the catheter to become disconnected from the reservoir. PMID:2944238

González-Darder, J; Alacreu, J B; Garcia-Vázquez, F



Cleavage of cystatin C in the cerebrospinal fluid of patients with multiple sclerosis  

Microsoft Academic Search

Objective: The diagnosis of multiple sclerosis (MS) can be challenging because of the lack of a specific diagnostic test. Recent advances in proteomics, however, offer new opportunities for biomarker discovery and the study of disease pathogenesis. Methods: We analyzed cerebrospinal fluid (CSF) samples from 29 patients with MS or clinically isolated syndromes (CIS), 27 patients with transverse myelitis (TM), 50

David N. Irani; Caroline Anderson; Rebekah Gundry; Robert Cotter; Stacy Moore; Douglas A. Kerr; Justin C. McArthur; Ned Sacktor; Carlos A. Pardo; Melina Jones; Peter A. Calabresi; Avindra Nath



Characteristic abnormalities in cerebrospinal fluid biochemistry in children with cerebral malaria compared to viral encephalitis  

Microsoft Academic Search

BACKGROUND: In developing countries where Plasmodium falciparum malaria is endemic, viral encephalitis and cerebral malaria are found in the same population, and parasitemia with Plasmodium falciparum is common in asymptomatic children. The objective of this study was to investigate the cerebrospinal fluid (CSF) biochemistry in children with cerebral malaria compared to those with presumed viral encephalitis. METHODS: We studied the

SR Jakka; S Veena; RM Atmakuri; M Eisenhut



MR Measurement of Cerebrospinal Fluid Velocity Wave Speed in the Spinal Canal  

Microsoft Academic Search

Noninvasive measurement of the speed with which the cerebrospinal fluid (CSF) velocity wave travels through the spinal canal is of interest as a potential indicator of CSF system pressure and compliance, both of which may play a role in the development of craniospinal diseases. However, measurement of CSF velocity wave speed (VWS) has eluded researchers primarily due to either a

Wojciech Kalata; Bryn A. Martin; John N. Oshinski; Michael Jerosch-Herold; Thomas J. Royston; Francis Loth



Cerebrospinal fluid corticotropin-releasing hormone in neurodegenerative diseases: Reduction in spinocerebellar degeneration  

Microsoft Academic Search

Levels of corticotropin-releasing hormone (CRH) in cerebrospinal fluid (CSF) were examined in patients with spinocerebellar degeneration (SCD) including olivopontocerebellar atrophy (OPCA), dentatorubropallidoluysian atrophy (DRPLA) and Friedreich's ataxia, Parkinson's disease (PD) and senile dementia of the Alzheimer type (SDAT), and normal aged subjects. CRH concentrations in CSF were significantly reduced in SCD compared to SDAT, PD and normal aged subjects. It

Shuso Suemaru; Koso Suemaru; Kensuke Kawai; Shinji Miyata; Keigo Nobukuni; Yuetsu Ihara; Reiko Namba; Katsuya Urakami; Kozo Hashimoto



Increased Cortisol in the Cerebrospinal Fluid of Women with Functional Hypothalamic Amenorrhea  

Microsoft Academic Search

Context: The proximate cause of functional hypothalamic amenor- rhea (FHA) is reduced GnRH drive. The concomitant increase in circulating cortisol suggests that psychogenic stress plays an etiologic role, but others have argued for a strictly metabolic cause, such as undernutrition or excessive exercise. Indeed, our finding that the cerebrospinal fluid (CSF) concentration of CRH was not elevated in FHA cast

Benedetta Brundu; Tammy L. Loucks; Lauri J. Adler; Judy L. Cameron; Sarah L. Berga



Cerebrospinal Fluid Tau Levels in Neurodegenerative Diseases with Distinct Tau-Related Pathology  

Microsoft Academic Search

Cerebrospinal fluid tau (CSF-tau) levels were quantified in 8 patients with frontotemporal dementia (FTD), 6 patients with progressive supranuclear palsy (PSP), 3 patients with corticobasal degeneration (CBD), and 6 patients with dementia with Lewy bodies (DLB). The CSF-tau levels were significantly increased in FTD and DLB, but not in PSP and CBD, compared to that previously reported in normal controls.

Hiroyuki Arai; Yu-ichi Morikawa; Makoto Higuchi; Toshifumi Matsui; Christopher M. Clark; Masakazu Miura; Nobuo Machida; Virginia M.-Y. Lee; John Q. Trojanowski; Hidetada Sasaki



Revised national guidelines for analysis of cerebrospinal fluid for bilirubin in suspected subarachnoid haemorrhage  

Microsoft Academic Search

It is crucially important to detect subarachnoid haemorrhage (SAH) in all patients in whom it has occurred to select patients for angiography and preventative surgery. A computerized tomography (CT) scan is positive in up to 98% of patients with SAH presenting within 12 h, but is positive in only 50% of those presenting within one week. Cerebrospinal fluid (CSF) bilirubin

Anne Cruickshank; Peter Auld; Robert Beetham; Gillian Burrows; William Egner; Ian Holbrook; Geoff Keir; Emma Lewis; Dina Patel; I. Watson; P. White



The JC virus antibody response in serum and cerebrospinal fluid in progressive multifocal leucoencephalopathy  

Microsoft Academic Search

Background: A clinical diagnosis of progressive multifocal leucoencephalopathy (PML) can be confirmed by histological or virological examination of brain material. Whilst a less invasive method is provided by the detection of JC DNA in cerebrospinal fluid (CSF), very few studies have been done to assess the value of JC virus (JCV) serology in PML diagnosis.Objectives: To study the JCV antibody

Wendy A. Knowles; Richard W. Luxton; Julian F. Hand; Sylvia D. Gardner; David W. G. Brown



Anisotropic equivalent conductivity tensors for bioelectric modeling of partial volume effects in cerebrospinal fluid spaces  

Microsoft Academic Search

Accurate modeling of bioelectric propagation within the head is necessary for precise electromagnetic source localization. We present here a new approach for modeling spaces fractionally composed of grey matter and cerebrospinal fluid. Using information about the orientation of the cortical surface, we construct anisotropic conductivity tensors to model the partial volume effects frequently present within sulci. Our results indicate that

Damon E. Hyde; Simon K. Warfield



Increase in ?-Amyloid Levels in Cerebrospinal Fluid of Children with Down Syndrome  

Microsoft Academic Search

Background: Individuals with Down syndrome (DS) invariably develop Alzheimer’s disease (AD) during their life span. It is therefore of importance to study young DS patients when trying to elucidate early events in AD pathogenesis. Aim: To investigate how levels of different amyloid-? (A?) peptides, as well as tau and phosphorylated tau, in cerebrospinal fluid (CSF) from children with DS change

Hillevi Englund; Göran Annerén; Jan Gustafsson; Ulrika Wester; Jens Wiltfang; Lars Lannfelt; Kaj Blennow; Kina Höglund



Can Cerebrospinal Fluid Uric Acid Levels Differentiate Intraventricular Hemorrhage from Traumatic Tap?  

Microsoft Academic Search

Objective: To measure blood and cerebrospinal fluid (CSF) uric acid (UA) levels of neonates with intraventricular hemorrhage (IVH), and to examine whether or not UA can be used to differentiate traumatic tap from IVH. Material and Methods: The control group (n = 19, group I) consisted of neonates presenting with signs requiring analysis of CSF but whose CSF indices proved

K. Mutlu Hayran



Epidural fibrin glue injection stops persistent cerebrospinal fluid leak during long-term intrathecal catheterization  

Microsoft Academic Search

he leakage of cerebrospinal fluid (CSF) during the initial phase of long-term intrathecal (IT) in- fusion of analgesics can be a bothersome com- plaint. A series of 98 cancer patients was treated with an IT catheter in this hospital in one year; 8% showed persistent leakage of CSF via the catheter tract. In a previous series, 26% of the patients

Bas M. Gerritse; Robert T. M. van Dongen; Ben J. P. Crul



Prevention of Cerebrospinal Fluid Leaks and Transtemporal Surgery of Acoustic Tumors  

PubMed Central

Postoperative cerebrospinal fluid (CSF) leaks continue to be a problem with transtemporal approaches to the cerebellopontine angle. In this article we describe a modification of the transotic technique, which has proved to be effective in preventing both leaks and subcutaneous collections of CSF. ImagesFigure 5

Kumar, Arvind; Siedentop, Karl H.



Plasma and cerebrospinal fluid pharmacokinetics of SU5416 after intravenous administration in nonhuman primates  

Microsoft Academic Search

Purpose SU5416 is a small, lipophilic synthetic molecule that selectively inhibits the tyrosine kinase activity of the VEGF receptor Flk-1\\/KDR. The role of this agent in brain tumors is currently being investigated. Pharmacokinetic studies of SU5416 have been performed in humans; however, there have been no studies of its penetration in the cerebrospinal fluid (CSF). We studied the pharmacokinetics of

Jamie Renbarger; Alexander Aleksic; Leticia McGuffey; Robert Dauser; Stacey Berg; Susan Blaney



A rapid and simple cannulation technique for repeated sampling of cerebrospinal fluid in freely moving rats  

Microsoft Academic Search

A cannulation technique for frequent sampling of cerebrospinal fluid (CSF) in unanaesthetized freely moving rats is described. A permanent stainless steel cannula, constructed in such a way that no loss of CSF occurs, is placed into the rat's cisterna magna and fixed to the skull by anchoring screws and dental cement. A special CSF outflow opening of the cannula is

H. J. Bouman; T. B. van Wimersma Greidanus



Prolonged Jackson-Pratt drainage in the management of lumbar cerebrospinal fluid leaks  

Microsoft Academic Search

BackgroundCerebrospinal fluid (CSF) leak is a complication of spinal surgery. Intraoperative or postoperative identification of a CSF leak often results in wound healing complications, lumbar drain placement, and\\/or reoperation. These complications usually extend a patient's hospital stay, can be painful, and have their own associated risks. The authors describe a technique that may improve on traditional interventions by managing postoperative

Samuel A. Hughes; Burak M. Ozgur; Michael German; William R. Taylor



Baseline Neuropsychological Profile and Cognitive Response to Cerebrospinal Fluid Shunting for Idiopathic Normal Pressure Hydrocephalus  

Microsoft Academic Search

Objective: To evaluate neurocognitive changes and predict neurocognitive outcome after ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus (INPH). Background: Reports of neurocognitive response to shunting have been variable and studies that predict cognitive outcomes after shunting are limited. We reviewed our experience with cognitive outcomes for INPH patients who were selected for shunting based on abnormal cerebrospinal fluid (CSF) pressure

George Thomas; Matthew J. McGirt; Graeme Woodworth; Jennifer Heidler; Daniele Rigamonti; Argye E. Hillis; Michael A. Williams



Increased hypocretin-1 levels in cerebrospinal fluid after REM sleep deprivation  

Microsoft Academic Search

Rat cisternal (CSF) hypocretin-1 in cerebrospinal fluid was measured after 6 or 96 h of REM sleep deprivation and following 24 h of REM sleep rebound. REM deprivation was found to increase CSF hypocretin-1 collected at zeitgeber time (ZT) 8 but not ZT0. Decreased CSF hypocretin levels were also observed at ZT8 after 24 h of REM sleep rebound. These

Mario Pedrazzoli; Vania D'almeidasupasu; Paulo J. f. Martins; Ricardo B. Machado; Lin Ling; Seiji Nishino; Sergio Tufik; Emmanuel Mignot



Elevated levels of tau-protein in cerebrospinal fluid of patients with Creutzfeldt–Jakob disease  

Microsoft Academic Search

Creutzfeldt–Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for tau-protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for

Markus Otto; Jens Wiltfang; Hayrettin Tumani; Inga Zerr; Maria Lantsch; Johannes Kornhuber; Thomas Weber; Hans A Kretzschmar; Sigrid Poser



Cerebrospinal fluid concentration of neuron-specific enolase in diagnosis of Creutzfeldt-Jakob disease  

Microsoft Academic Search

Neuron-specific enolase (NSE) is among the biochemical markers in cerebrospinal fluid reported to be useful in the differential diagnosis of Creutzfeldt-Jakob disease from other dementing illnesses. In a group of 58 patients with definite and probable Creutzfeldt-Jakob disease, NSE concentrations (median 94·0, interquartile range 256 ng\\/mL) were significantly higher (p

I. Zerr; M. Bodemer; S. Räcker; S. Grosche; S. Poser; T. Weber; H. A. Kretzschmar



Plasma and cerebrospinal fluid pharmacokinetics of depsipeptide (FR901228) in nonhuman primates  

Microsoft Academic Search

Purpose Acetylation of histones by histone acetyl transferases (HATs) leads to transcriptional activation, while histone deacetylase (HDAC) activity leads to transcriptional repression. Abnormalities of histone acetylation are associated with the malignant phenotype. Depsipeptide (FR901228) inhibits HDAC and has shown anticancer activity in preclinical models. We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of depsipeptide in a nonhuman primate model

Stacey L. Berg; Jeffery Stone; Jim J. Xiao; Kenneth K. Chan; Jed Nuchtern; Robert Dauser; Leticia McGuffey; Patrick Thompson; Susan M. Blaney



Elevation of Cerebrospinal Fluid Protein in Patients with Diabetes Mellitus Is Associated with Duration of Diabetes  

Microsoft Academic Search

We investigated the relationships between total cerebrospinal fluid (CSF) protein in diabetic patients and the clinical characteristics of diabetes mellitus. The subjects comprised 16 diabetic patients (median age = 60.5 years, range = 47–71) who were studied retrospectively. Patients with diseases known to be associated with increases in total CSF protein were excluded as far as possible. The median total

Hiroshi Kobessho; Kenichi Oishi; Hirotoshi Hamaguchi; Fumio Kanda



Polymerase chain reaction (PCR) for rapid detection of cerebrospinal fluid shunt or ventriculostomy infections  

Microsoft Academic Search

Introduction: Infections of cerebrospinal fluid (CSF) shunts or ventriculostomies are common complications that are associated with significant morbidity and mortality. Detection of infection may be difficult or delayed as it requires colonial growth of microorganisms in culture medium. PCR provides rapid and accurate detection of bacterial DNA.Methods: Under Institutional Review Board approval (X030403011), 50 samples of CSF samples were collected

Jason T. Banks; Charles L. Wolff; Suman Bharara; Jeffrey P. Blount; R. Shane Tubbs; G. Yancey Gillespie; James M. Markert



Normalization of Serum Rapid Plasma Reagin Titer Predicts Normalization of Cerebrospinal Fluid and Clinical Abnormalities after Treatment of Neurosyphilis  

PubMed Central

Background Success of neurosyphilis treatment is defined by normalization of cerebrospinal fluid (CSF) and clinical abnormalities. The goal of this study was to determine whether normalization of serum rapid plasma reagin (RPR) titer could accurately predict treatment success. Methods One hundred ten patients who were enrolled in a longitudinal study of CSF abnormalities in syphilis had asymptomatic syphilitic meningitis, symptomatic syphilitic meningitis, or syphilitic eye disease and were treated for neurosyphilis. At 4, 7, and 13 months after treatment, serum RPR titer and CSF and clinical abnormalities were analyzed for normalization. Odds ratios for normalization of each CSF and clinical abnormality when serum RPR titer had normalized and the positive predictive value of normalization of serum RPR titer for normalization of CSF and clinical abnormalities were determined. Results Serum RPR titer had normalized in 63 patients (57%) by 4 months after treatment, in 94 (85%) by 7 months, and in 97 (88%) by 13 months. Except for CSF protein concentration, normalization of serum RPR titer predicted normalization of other CSF and clinical abnormalities in >80% of patients at 4 months, >85% at 7 months, and >90% at 13 months. The odds of normalization of CSF and clinical abnormalities were 28–57-fold higher when serum RPR titer had normalized, compared with when it had not. Normalization of serum RPR titer was consistently less accurate in predicting treatment success in human immunodeficiency virus–infected patients who were not receiving antiretroviral therapy, compared with those who were receiving such therapy. Conclusions In most instances, normalization of serum RPR titer correctly predicts success of treatment of neurosyphilis, and follow-up lumbar puncture can be avoided.

Marra, Christina M.; Maxwell, Clare L.; Tantalo, Lauren C.; Sahi, Sharon K.; Lukehart, Sheila A.



Cerebrospinal fluid biomarkers in Guillain-Barré syndrome – Where do we stand?  

Microsoft Academic Search

\\u000a Abstract\\u000a   Guillain-Barré syndrome (GBS) is an acute inflammatory polyneuropathy affecting the myelin-protein sheathing and the axons\\u000a themselves to various degrees. Damage to these structures causes biomarkers to be released into the adjacent body fluid compartment.\\u000a In case of the proximal nerve roots these biomarkers diffuse into the cerebrospinal fluid (CSF). Here we review the literature\\u000a on CSF biomarkers in GBS,

Johannes Brettschneider; Axel Petzold; Sigurd Süssmuth; Hayrettin Tumani



Management of Persistent Cerebrospinal Fluid Leakage Following Thoraco-lumbar Surgery  

PubMed Central

Study Design This was a retrospective study of patients who had developed a dural tear after thoracic and lumbar spine surgery that was not recognized during the surgery, and was treated either by lumbar drainage or over-sewing of the wounds. Purpose To revisit the treatment strategies in postoperative dural leaks and present our experience with over-sewing of the wound and lumbar drainage. Overview of Literature Unintended durotomy is a frequent complication of spinal surgery. Management of subsequent cerebrospinal fluid leakage remains controversial. There is no distinct treatment guideline according to the etiology in the current literature. Methods The records of 368 consecutive patients who underwent thoracic and/or lumbar spine surgery from 2006 throug h 2010 were retrospectively reviewed. Seven cerebrospinal fluid fistulas and five pseudomeningoceles were noted in 12 (3.2%) procedures. Cerebrospinal fluid diversion by lumbar drainage in five pseudomeningoceles and over-sewing of wounds in seven cerebrospinal fluid fistulas employed in 12 patients. Clinical grading was evaluated by Wang. Results Of the 12 patients who had a dural tear, 5 were managed successfully with lumbar drainage, and 7 with oversewing of the wound. The clinical outcomes were excellent in 9 patients, good in 2, and poor in 1. Complications such as neurological deficits, or superficial or deep wound infections did not develop. A recurrence of the fistula or pseudomeningocele after the treatment was not seen in any of our patients. Conclusions Pseudomeningoceles respond well to lumbar drainage, whereas over-sewing of the wound is an alternative treatment option in cerebrospinal fluid fistulas without neurological compromise.

Ilbay, Konuralp; Kim, Michael Sun Min; Selek, Ozgur



Ventriculoperitoneal shunt malfunction from cerebrospinal fluid eosinophilia in children: case-based update  

Microsoft Academic Search

Introduction  Malfunction of cerebrospinal shunts is common and is due to multiple etiologies ranging from obstruction due to infiltrated\\u000a brain tissue to mechanical disconnection.\\u000a \\u000a \\u000a \\u000a \\u000a Discussion  We review the differential diagnosis and recommended evaluation and treatment for cerebrospinal fluid (CSF) eosinophilia.\\u000a \\u000a \\u000a \\u000a Illustrative case  We report a child who, following the use of an antibiotics-impregnated ventricular catheter, developed sterile ventriculoperitoneal\\u000a shunt malfunction thought to be

R. Shane Tubbs; Mitchel Muhleman; Marios Loukas; Aaron A. Cohen-Gadol


Pathogenesis and pathophysiology of bacterial meningitis.  

PubMed Central

Bacterial meningitis remains a disease with associated unacceptable morbidity and mortality rates despite the availability of effective bactericidal antimicrobial therapy. Through the use of experimental animal models of infection, a great deal of information has been gleaned concerning the pathogenic and pathophysiologic mechanisms operable in bacterial meningitis. Most cases of bacterial meningitis begin with host acquisition of a new organism by nasopharyngeal colonization followed by systemic invasion and development of a high-grade bacteremia. Bacterial encapsulation contributes to this bacteremia by inhibiting neutrophil phagocytosis and resisting classic complement-mediated bactericidal activity. Central nervous system invasion then occurs, although the exact site of bacterial traversal into the central nervous system is unknown. By production and/or release of virulence factors into and stimulation of formation of inflammatory cytokines within the central nervous system, meningeal pathogens increase permeability of the blood-brain barrier, thus allowing protein and neutrophils to move into the subarachnoid space. There is then an intense subarachnoid space inflammatory response, which leads to many of the pathophysiologic consequences of bacterial meningitis, including cerebral edema and increased intracranial pressure. Attenuation of this inflammatory response with adjunctive dexamethasone therapy is associated with reduced concentrations of tumor necrosis factor in the cerebrospinal fluid, with diminished cerebrospinal fluid leukocytosis, and perhaps with improvement of morbidity, as demonstrated in recent clinical trials. Further information on the pathogenesis and pathophysiology of bacterial meningitis should lead to the development of more innovative treatment and/or preventive strategies for this disorder. Images

Tunkel, A R; Scheld, W M



Cerebrospinal fluid creatine kinase in acutely psychotic patients 1  

PubMed Central

Significantly elevated serum creatine phosphokinase concentrations have been demonstrated in 70% of patients with acute psychosis. Elevations in spinal fluid creatine phosphokinase (CPK) activity have been reported in several neurological diseases, often in association with otherwise normal routine spinal fluid studies. Spinal fluid and serum were obtained simultaneously from 11 patients with acute psychosis, the majority being schizophrenic. Although the serum CPK was elevated in eight of the 11 subjects, spinal fluid glucose, protein, colloidal gold, and CPK were normal in all cases. The theoretical implications of these results are discussed.

Martin, William A.; Garey, Richard E.; Heath, Robert G.



PCR and Electrospray Ionization Mass Spectrometry for Detection of Persistent Enterococcus faecalis in Cerebrospinal Fluid following Treatment of Postoperative Ventriculitis.  


We describe the use of PCR and electrospray ionization followed by mass spectrometry (PCR/ESI-MS) to evaluate "culture-negative" cerebrospinal fluid (CSF) from a 67-year-old man who developed postoperative bacterial ventriculitis following a suboccipital craniotomy for resection of an ependymoma in the 4th ventricle. CSF samples were obtained on seven occasions, beginning in the operating room at the time of insertion of a right ventriculoperitoneal shunt (VPS) and continuing until his death, 6 weeks later. During the course of the illness, two initial CSF specimens taken before the initiation of antimicrobial treatment were notable for growth of Enterococcus faecalis. Once antimicrobial treatment was initiated, all CSF cultures were negative. PCR/ESI-MS detected genetic evidence of E. faecalis in all CSF samples, but the level of detection (LOD) decreased once antimicrobial treatment was initiated. When our patient returned with symptoms of meningitis 3 days after the completion of antibiotic treatment, CSF cultures remained negative, but PCR/ESI-MS again found genetic evidence for E. faecalis at levels comparable to the pretreatment levels seen initially. This unique case and these findings suggest that determination of CSF LOD by PCR/ESI-MS may be a very sensitive indicator of persistent infection in patients on antibiotic therapy for complex CNS infections and may have relevance for treatment duration and assessment of persistent or recurrent infection at the completion of therapy. PMID:23903548

Farrell, John J; Tsung, Andrew J; Flier, Lisa; Martinez, Derek L; Beam, Sarah B; Chen, Clifford; Lowery, Kristin S; Sampath, Rangarajan; Bonomo, Robert A



Is cerebrospinal fluid drainage of benefit to neuroprotection in patients undergoing surgery on the descending thoracic aorta or thoracoabdominal aorta?  

PubMed Central

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was ‘Is cerebrospinal fluid (CSF) drainage of benefit in patients undergoing surgery on the descending thoracic aorta or thoracoabdominal aorta?’ Altogether 1177 papers were found using the reported search, of which 17 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Ten of 13 studies demonstrate significant neurological protection from CSF drainage (±additional adjuncts), with two further papers showing no significant difference between patients who had or had not had CSF drainage and one study unable to provide any conclusions. For patients having surgery on the thoracic aorta or thoracoabdominal aorta CSF drainage, maintaining pressures <10 mmHg (P < 0.03), in conjunction with other neuroprotective strategies, minimizes the risk of neurological sequelae when compared with patients treated with similar adjuncts but without CSF drainage. The majority of studies used additional neuroprotective strategies, including cooling and reattachment of the intercostal arteries as adjuncts to CSF drainage. Logistic regression curves demonstrated that the longer the ischaemia time, the greater the benefit from CSF drainage (P < 0.04). Four papers observed complications of CSF drainage, of which the main complications were: catheter occlusion or dislodgement, headache, meningitis and subdural haematoma. Overall, CSF drainage does offer a neuroprotective benefit; preventing paraplegia if CSF pressures are maintained <10 mmHg.

Bilal, Haris; O'Neill, Bridie; Mahmood, Sarah; Waterworth, Paul



Embryonic cerebrospinal fluid regulates neuroepithelial survival, proliferation, and neurogenesis in chick embryos.  


Early in development, the behavior of neuroepithelial cells is controlled by several factors, which act in a developmentally regulated manner. Diffusible factors are secreted locally by the neuroepithelium itself, although other nearby structures may also be involved. Evidence suggests a physiological role for the cerebrospinal fluid in the development of the brain. Here, using organotypic cultures of chick embryo neuroepithelial explants from the mesencephalon, we show that the neuroepithelium in vitro is not able to self-induce cell survival, replication, and neurogenesis. We also show that the embryonic cerebrospinal fluid (E-CSF) promotes neuroepithelial stem cell survival and induces proliferation and neurogenesis in mesencephalic explants. These data strongly suggest that E-CSF is involved in the regulation of neuroepithelial cells behavior, supporting the hypothesis that this fluid plays a key role during the early development of the central nervous system. PMID:15803475

Gato, Angel; Moro, J A; Alonso, M I; Bueno, D; De La Mano, A; Martín, C



Pyogenic meningitis in Ahmedabad.  


One hundred and thirty five cerebrospinal fluid (CSF) samples from children clinically diagnosed Pyogenic meningitis (in and around Ahmedabad) were subjected to physical, bacteriological, cytological and biochemical examinations. It was found that all CSF specimens were turbid, the culture positivity varied form 12.12 to 56%. The highest percentage was found in children of less than one year of age. The average percentage of culture positivity was 28.68%. The result of gram stain was more than that of cultural examination. Gram stain of CSF was specific, accurate and highly valuable in the diagnosis of pyogenic meningitis. Among gram positive organisms isolated, Staphylococcus aureus was highest (8.8%) followed by Diplococcus pneumoniae (3.7%), but Klebsiella was predominant (6.6%) among gram negative bacilli. Staph. aureus was 100% sensitive to erythromycin, gentamycin, kanamycin and ampicillin. The results of cytological and biochemical tests correlated (67.1%). There was increase in polymorphs and protein, sugar levels decreased. PMID:8157337

Panjarathinam, R; Shah, R K


Use of Quantitative Broad-based Polymerase Chain Reaction for Detection and Identification of Common Bacterial Pathogens in Cerebrospinal Fluid  

PubMed Central

Background Conventional laboratory diagnosis of bacterial meningitis based on microscopy followed by culture is time-consuming and has only moderate sensitivity. Objectives The objective was to define the limit of detection (LOD), analytic specificity, and performance characteristics of a broad-based quantitative multiprobe polymerase chain reaction (PCR) assay for rapid bacterial detection and simultaneous pathogen-specific identification in patients with suspected meningitis. Methods A PCR algorithm consisting of initial broad-based detection of Eubacteriales by a universal probe, followed by pathogen identification using either pathogen-specific probes or Gram-typing probes, was employed to detect pathogens. The 16S rRNA gene, which contains both conserved and variable regions, was chosen as the target. Pathogen-specific probes were designed for Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae, Staphylococcus epidermidis, Staphylococcus aureus, Escherichia coli, and Listeria monocytogenes. Gram-positive and -negative typing probes were designed based on conserved regions across all eubacteria. The LOD and time to detection were assessed by dilutional mocked-up samples. A total of 108 convenience cerebrospinal fluid (CSF) clinical samples obtained from the Johns Hopkins Hospital (JHH) microbiology laboratory were tested, and results were compared with hospital microbiologic culture reports. Results The LOD of the assay ranged from 101 to 102 colony-forming units (CFU) / mL. Pathogen-specific probes showed no cross-reactivity with other organisms. Time to detection was 3 hours. In clinical specimens, the universal probe correctly detected 16 of 22 culture-positive clinical specimens (sensitivity = 72.7%; 95% confidence interval [CI] = 49.8% to 89.3%), which were all correctly characterized by either pathogen-specific or Gram-typing probes. Adjusted sensitivity after removing probable microbiologic laboratory contaminants was 88.9% (95% CI = 65.3% to 98.6%). The universal probe was negative for 86 of 86 culture-negative specimens. Conclusions A broad-based multiprobe PCR assay demonstrated strong analytic performance characteristics. Findings from a pilot clinical study showed promise in translation to human subjects, supporting potential utility of the assay as an adjunct to traditional diagnostics for early identification of bacterial meningitis.

Rothman, Richard; Ramachandran, Padmini; Yang, Samuel; Hardick, Andrew; Won, Helen; Kecojevic, Aleksandar; Quianzon, Celeste; Hsieh, Yu-Hsiang; Gaydos, Charlotte



Bacterial meningitis: new therapeutic approaches.  


Bacterial meningitis remains a disease with high mortality and long-term morbidity. Outcome critically depends on the rapid initiation of effective antibiotic therapy. Since a further increase of the incidence of pathogens resistant to antibacterials can be expected both in community-acquired and nosocomial bacterial meningitis, the choice of an optimum initial empirical antibiotic regimen will gain significance. In this context, the use of antibiotics which are bactericidal but do not lyse bacteria, may emerge as a therapeutic option. Conversely, the role of corticosteroids, which decrease the entry of hydrophilic antibacterials into the cerebrospinal fluid, as adjunctive therapy will probably decline as a consequence of the increasing antibiotic resistance of bacteria causing meningitis. Consequent vaccination of all children at present is the most efficient manner to reduce disease burden. PMID:24073921

Nau, Roland; Djukic, Marija; Spreer, Annette; Eiffert, Helmut



A Novel Unbiased Proteomic Approach to Detect the Reactivity of Cerebrospinal Fluid in Neurological Diseases*  

PubMed Central

Neurodegenerative diseases, such as multiple sclerosis represent global health issues. Accordingly, there is an urgent need to understand the pathogenesis of this and other central nervous system disorders, so that more effective therapeutics can be developed. Cerebrospinal fluid is a potential source of important reporter molecules released from various cell types as a result of central nervous system pathology. Here, we report the development of an unbiased approach for the detection of reactive cerebrospinal fluid molecules and target brain proteins from patients with multiple sclerosis. To help identify molecules that may serve as clinical biomarkers for multiple sclerosis, we have biotinylated proteins present in the cerebrospinal fluid and tested their reactivity against brain homogenate as well as myelin and myelin-axolemmal complexes. Proteins were separated by two-dimensional gel electrophoresis, blotted onto membranes and probed separately with biotinylated unprocessed cerebrospinal fluid samples. Protein spots that reacted to two or more multiple sclerosis-cerebrospinal fluids were further analyzed by matrix assisted laser desorption ionization-time-of-flight time-of-flight mass spectrometry. In addition to previously reported proteins found in multiple sclerosis cerebrospinal fluid, such as ?? crystallin, enolase, and 14–3-3-protein, we have identified several additional molecules involved in mitochondrial and energy metabolism, myelin gene expression and/or cytoskeletal organization. These include aspartate aminotransferase, cyclophilin-A, quaking protein, collapsin response mediator protein-2, ubiquitin carboxy-terminal hydrolase L1, and cofilin. To further validate these findings, the cellular expression pattern of collapsin response mediator protein-2 and ubiquitin carboxy-terminal hydrolase L1 were investigated in human chronic-active MS lesions by immunohistochemistry. The observation that in multiple sclerosis lesions phosphorylated collapsin response mediator protein-2 was increased, whereas Ubiquitin carboxy-terminal hydrolase L1 was down-regulated, not only highlights the importance of these molecules in the pathology of this disease, but also illustrates the use of our approach in attempting to decipher the complex pathological processes leading to multiple sclerosis and other neurodegenerative diseases.

Menon, Krishnakumar N.; Steer, David L.; Short, Martin; Petratos, Steven; Smith, Ian; Bernard, Claude C. A.



Use of cerebrospinal fluid biomarkers in clinical trials for schizophrenia and depression.  


The pharmaceutical industry is increasingly using biomarkers in clinical trials in order to determine if new drug candidates are displaying the expected pharmacological properties and to give early indications if they are showing efficacy or unexpected toxicity. This is especially true for the development of new drug candidates for psychiatric disorders such as schizophrenia and depression, where it is imperative to understand whether the drug is reaching the brain and acting on the target. A particular challenge for biochemical biomarkers used to determine centrally mediated activity is the relative inaccessibility of the brain to direct sampling of cells or tissues. As a result, the use of biomarkers located in the cerebrospinal fluid and in close contact with the interstitial fluid of the brain has risen in prominence. Cerebrospinal fluid biomarkers allow for the analysis of biochemical changes that reflect pharmacological activity or that may be related to the disease. In the area of psychiatric disorders, many studies have utilized biochemical biomarkers in the cerebrospinal fluid for gaining pharmacodynamic or disease modification information. This review summarizes many of these efforts, and identifies challenges and opportunities for utilizing biomarkers for new drug candidates targeting psychiatric disorders. PMID:22296205

Wan, Hong I; Soares, Holly; Waring, Jeffrey F



Leukemic and lymphomatous meningitis: incidence, prognosis and treatment  

Microsoft Academic Search

Summary Neoplastic meningitis (NM) is a common problem in neuro-oncology occurring in approximately 5% of all patients with cancer. Notwithstanding frequent focal signs and symptoms in NM, NM is a disease affecting the entire neuraxis and therefore staging and treatment need encompass all cerebrospinal fluid (CSF) compartments. Central nervous system (CNS) staging of NM includes contrast enhanced cranial computerized tomography

Marc C. Chamberlain; Craig Nolan; Lauren E. Abrey



Burr Hole Drainage : Could Be Another Treatment Option for Cerebrospinal Fluid Leakage after Unidentified Dural Tear during Spinal Surgery?  

PubMed Central

Authors report a rare case of acute intracranial subdural and intraventricular hemorrhage that were caused by intracranial hypotension resulted from cerebrospinal fluid leakage through an unidentified dural tear site during spinal surgery. The initial brain computed tomography image showed acute hemorrhages combined with preexisting asymptomatic chronic subdural hemorrhage. One burr hole was made over the right parietal skull to drain intracranial hemorrhages and subsequent drainage of cerebrospinal fluid induced by closure of the durotomy site. Among various methods to treat cerebrospinal fluid leakage through unidentified dural injury site, primary repair and spinal subarachnoid drainage are well known treatment options. The brain imaging study to diagnose intracranial hemorrhage should be taken before selecting the treatment method, especially for spinal subarachnoid drainage. Similar mechanism to its spinal counterpart, cranial cerebrospinal fluid drainage has not been mentioned in previous article and could be another treatment option to seal off an unidentified dural tear in particular case of drainage of intracranial hemorrhage is needed.



Stanthrdization of theCoomassie BlueMethodforCerebrospinal FluidProteins  

Microsoft Academic Search

Coomassie Brilliant Blue G-250 can be used to quantita- tively determine proteins in cerebrospinal fluid. Whenthe dye combines with protein, the absorption maximum of the dye shifts. The dye-protein color forms almost instanta- neously and is stable for at least 1 h. The procedure is also insensitive to changes in temperature in the range of 20-30 #{176}C. The absorptivities of



2?, 3?Cyclic nucleotide 3?-phosphodiesterase activity in the cerebrospinal fluid of patients with demyelinating diseases  

Microsoft Academic Search

We aimed to study the level of CNPase activity in the cerebrospinal fluid of patients with demyelinating diseases and other\\u000a neurological diseases, particularly multiple sclerosis, with reference to CSF myelin basic protein content. CNPase activity\\u000a was measured paper chromatographically using radioactive 2?,3?-cAMP as a substrate. Myelin basic protein content was measured\\u000a with a radioimmunoassay. The mean level of CNPase activity

Haruhiko Suda; Takeshi Hosokawa; Ryozo Ohno; Kastuhiko Hamaguchi; Yasuzo Tsukada



Neopterin and biopterin concentrations in cerebrospinal fluid in controls less than 1 year old  

Microsoft Academic Search

Neopterin and biopterin concentrations were measured in cerebrospinal fluid (CSF) and urine samples from controls less than 1 year old. This is the first time for CSF reference data for controls less than 1 year old to be reported. The ratio of neopterin to biopterin in CSF 0–30 days (n=48) of age in control samples was 0.65±0.31 (SD), which was

Yoshitomo Sawada; Haruo Shintaku; Gen Isshiki



Technical and biochemical factors affecting cerebrospinal fluid 5-MTHF, biopterin and neopterin concentrations  

Microsoft Academic Search

Background: The diagnosis of pediatric neurologic disorders with a deficiency in the biosynthesis of either the neurotransmitters serotonin and dopamine, or the co-factor tetrahydrobiopterin or a cerebral 5-methyltetrahydrofolate (5-MTHF) deficiency, strongly relies on a robust analysis of neurotransmitter metabolites, pterins and 5-MTHF in the cerebrospinal fluid (CSF). The aim of this study was to investigate which technical and biochemical factors

M. M. Verbeek; A. M. Blom; R. A. Wevers; A. J. Lagerwerf; J. van de Geer; M. A. A. P. Willemsen



Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome  

Microsoft Academic Search

BackgroundNeurologic Post Treatment Lyme disease (nPTLS) and Chronic Fatigue (CFS) are syndromes of unknown etiology. They share features of fatigue and cognitive dysfunction, making it difficult to differentiate them. Unresolved is whether nPTLS is a subset of CFS.Methods and Principal FindingsPooled cerebrospinal fluid (CSF) samples from nPTLS patients, CFS patients, and healthy volunteers were comprehensively analyzed using high-resolution mass spectrometry

Steven E. Schutzer; Thomas E. Angel; Tao Liu; Athena A. Schepmoes; Therese R. Clauss; Joshua N. Adkins; David G. Camp; Bart K. Holland; Jonas Bergquist; Patricia K. Coyle; Richard D. Smith; Brian A. Fallon; Benjamin H. Natelson; Howard Gendelman



Detection of cancer cells in the cerebrospinal fluid: current methods and future directions  

Microsoft Academic Search

The spread of cancer into the central nervous system is a serious problem leading to neurological symptoms and rapid mortality.\\u000a The current tools available for detecting the spread of cancer into the cerebrospinal fluid (CSF) are cytology, neurologic\\u000a examination, and neuroimaging. All three of these methods can be applied in concert to reach a diagnosis, but they all suffer\\u000a from

Cody L Weston; Michael J Glantz; James R Connor



Cerebrospinal fluid proteomic patterns discriminate Parkinson's disease and multiple system atrophy.  


The differential diagnosis of Parkinson's disease and multiple system atrophy can be challenging, especially in the early stages of the diseases. We developed a proteomic profiling strategy for parkinsonian diseases using mass spectrometry analysis for magnetic-bead-based enrichment of cerebrospinal fluid peptides/proteins and subsequent multivariate statistical analysis. Cerebrospinal fluid was obtained from 37 patients diagnosed with Parkinson's disease, 32 patients diagnosed with multiple system atrophy, and 26 patients diagnosed with other neurological diseases as controls. The samples were from the first cohort and the second cohort. Cerebrospinal fluid peptides/proteins were purified with C8 magnetic beads, and spectra were obtained by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Principal component analysis and support vector machine methods are used to reduce dimension of the data and select features to classify diseases. Cerebrospinal fluid proteomic profiles of Parkinson's disease, multiple system atrophy, and control were differentiated from each other by principal component analysis. By building a support vector machine classifier, 3 groups were classified effectively with good cross-validation accuracy. The model accuracy was well preserved for both cases, training by the first cohort and validated by the second cohort and vice versa. Receiver operating characteristics proved that the peak of m/z 6250 was the most important to differentiate multiple system atrophy from Parkinson's disease, especially in the early stages of the disease. A proteomic pattern classification method can increase the accuracy of clinical diagnosis of Parkinson's disease and multiple system atrophy, especially in the early stages. PMID:22674850

Ishigami, Noriko; Tokuda, Takahiko; Ikegawa, Masaya; Komori, Mika; Kasai, Takashi; Kondo, Takayuki; Matsuyama, Yumiko; Nirasawa, Takashi; Thiele, Herbert; Tashiro, Kei; Nakagawa, Masanori



Phosphorylated tau in cerebrospinal fluid as a marker for Creutzfeldt–Jakob disease  

Microsoft Academic Search

Objective: To determine the concentrations of microtubule associated protein tau and multiple phosphorylated tau epitopes in the cerebrospinal fluid of patients with sporadic Creutzfeldt–Jakob disease (sCJD), dementias, and controls, in order to evaluate their diagnostic use and clinical relevance.Methods: The CSF concentrations of total tau and phosphorylated tau at epitope 181 were determined by enzyme linked immunosorbent assay in 66

B Van Everbroeck; A J E Green; E Vanmechelen; H Vanderstichele; P Pals; R Sanchez-Valle; N Cuadrado Corrales; J-J Martin; P Cras



Peptide repertoire of human cerebrospinal fluid: novel proteolytic fragments of neuroendocrine proteins  

Microsoft Academic Search

Polypeptides in human cerebrospinal fluid (CSF), isolated by phase separation in chloroform–methanol–water and reversed-phase HPLC, were characterised by sequence analysis and mass spectrometry. This identified the presence of peptide fragments of testican, neuroendocrine specific protein VGF, neuroendocrine protein 7B2, chromogranin B\\/secretogranin I, chromogranin A, osteopontin, IGF-II E-peptide and proenkephalin. The majority of these fragments were generated by proteolysis at dibasic

Margareta Stark; Olle Danielsson; William J. Griffiths; Hans Jörnvall; Jan Johansson



Phytoestrogens and thyroid hormone levels in the cerebrospinal fluid of ewes fed red clover silage  

Microsoft Academic Search

In sheep, phytoestrogens are known to act at various levels on the hypothalamo–pituitary–gonadal axis, as well as the hypothalamo–pituitary–thyroid axis. The levels of genistein and daidzein and their metabolites, p-ethylphenol and equol, in the cerebrospinal fluid (CSF) were studied in ewes fed red clover silage. Moreover, to test the hypothesis that phytoestrogens may affect the access of thyroid hormones in

J. Skipor; T. Misztal; M. Pisku?a; W. Wiczkowski; J.-C. Thiéry


Failure of cerebrospinal fluid shunts: part II: overdrainage, loculation, and abdominal complications.  


Complications from cerebrospinal fluid shunts are common and can present with a variety of signs and symptoms. In this second part of a two-part review, shunt overdrainage, loculation of the ventricular system in patients with shunts, and abdominal complications related to ventriculoperitoneal shunts are discussed. Familiarity with these types of shunt failure is essential for neurologists and pediatricians because they are often the first to evaluate and triage these children. PMID:16504785

Browd, Samuel R; Gottfried, Oren N; Ragel, Brian T; Kestle, John R W



Clinical significance of cerebrospinal fluid nitric oxide concentrations in degenerative cervical and lumbar diseases  

Microsoft Academic Search

In animal models of degenerative lumbar disease, inducible nitric oxide synthase (iNOS) is expressed in macrophages and Schwann\\u000a cells following compression of the cauda equina. We previously reported that NO metabolites (nitrite plus nitrate: [NOx])\\u000a in the cerebrospinal fluid (CSF) correlate with postoperative pain relief in patients with degenerative lumbar disease and\\u000a with neurologic recovery rate postoperatively or after conservative

Hiroshi Denda; Shinji Kimura; Akiyoshi Yamazaki; Noboru Hosaka; Yuichi Takano; Kenji Imura; Yoichi Yajiri; Naoto Endo



Evaluation of Cerebrospinal Fluid Tau\\/Beta-Amyloid(42) Ratio as Diagnostic Markers for Alzheimer Disease  

Microsoft Academic Search

Background: Alzheimer’s disease (AD) is the leading cause of dementia. Currently, no definitive diagnostic test for AD exists. Cerebrospinal fluid (CSF) concentrations of amyloid ? (A?1-42) peptides and total tau proteins (T-tau) may serve as biomarkers for AD. Aim: The objective of this study was to investigate the usefulness of CSF A?1-42 and T-tau analyses in the diagnosis of AD

Mohamed Ali Smach; Bassem Charfeddine; Leila Ben Othman; Turkia Lammouchi; Hedi Dridi; Souhir Nafati; Afef Ltaief; Soufien Bennamou; Khalifa Limem



No increase in cerebrospinal fluid tau protein levels in patients with vascular dementia  

Microsoft Academic Search

Tau protein levels in cerebrospinal fluid (CSF-tau) were determined in 29 patients with old cerebrovascular disease (CVD, 21 demented and eight non-demented), 69 patients with Alzheimer's disease (AD) and 17 age-matched normal controls. The CSF-tau level in the vascular dementia (VD) group (24.0±17.0 pg\\/ml) was significantly lower (P<0.0001) than that in the AD group (90.0±45.3 pg\\/ml), but not significantly different

Hiroyuki Arai; Takuma Satoh-Nakagawa; Makoto Higuchi; Yu-ichi Morikawa; Masakazu Miura; Hisako Kawakami; Hisatomo Seki; Sadao Takase; Hidetada Sasaki



Proteomics Comparison of Cerebrospinal Fluid of Relapsing Remitting and Primary Progressive Multiple Sclerosis  

Microsoft Academic Search

BackgroundBased on clinical representation of disease symptoms multiple sclerosis (MScl) patients can be divided into two major subtypes; relapsing remitting (RR) MScl (85–90%) and primary progressive (PP) MScl (10–15%). Proteomics analysis of cerebrospinal fluid (CSF) has detected a number of proteins that were elevated in MScl patients. Here we specifically aimed to differentiate between the PP and RR subtypes of

Marcel P. Stoop; Vaibhav Singh; Lennard J. Dekker; Mark K. Titulaer; Christoph Stingl; Peter C. Burgers; Peter A. E. Sillevis Smitt; Rogier Q. Hintzen; Theo M. Luider



Neuronal targets of serum and cerebrospinal fluid autoantibodies in amyotrophic lateral sclerosis  

Microsoft Academic Search

Sera and cerebrospinal fluid (CSF) from 25 patients with amyotrophic lateral sclerosis (ALS) were tested by immunofluorescence\\u000a on fetal, juvenile and adult central and peripheral neuronal (CNS\\/PNS) tissues and on nerve biopsy material from affected\\u000a patients for the presence of autoantibodies. Results were compared with control sera from normal blood donors (n = 45) and patients with other neurological diseases

Axel Greiner; Bernd Schmaußer; Klaus Petzold; Hans Krüger; Alexander Marx



Tamoxifen Paradoxically Decreases Paclitaxel Deposition into Cerebrospinal Fluid of Brain Tumor Patients  

Microsoft Academic Search

Summary  Background: P-glycoprotein (Pgp) mediates, in part, resistance to natural product chemotherapy drugs which constitute over half of the\\u000a available drugs for cancer treatment. Tamoxifen (TAM) enhances intracellular deposition of natural product chemotherapy in\\u000a human cell lines by inhibition of Pgp. Pgp is highly expressed in the choroid plexus and is thought to be a key component\\u000a of the blood–cerebrospinal fluid

Johnson Chen; Casilda Balmaceda; Jeffrey N. Bruce; Michael B. Sisti; May Huang; Ying Kuen K. Cheung; Guy M. McKhann; Robert R. Goodman; Robert L. Fine



Proteome analysis of cerebrospinal fluid in Guillain–Barré syndrome (GBS)  

Microsoft Academic Search

We used two-dimensional difference in-gel electrophoresis (2-D-DIGE) for proteome analysis of cerebrospinal fluid (CSF) in Guillain–Barré syndrome (GBS). Spots showing >2-fold difference between GBS and controls were analysed using MALDI-TOF mass spectrometry.Proteins that were up-regulated in GBS included haptoglobin, serine\\/threonine kinase 10, ?-1-antitrypsin, SNC73, alpha II spectrin, IgG kappa chain and cathepsin D preprotein, while transferrin, caldesmon, GALT, human heat

V. Lehmensiek; S. D. Süssmuth; J. Brettschneider; G. Tauscher; S. Felk; F. Gillardon; H. Tumani



The narcoleptic borderland: a multimodal diagnostic approach including cerebrospinal fluid levels of hypocretin-1 (orexin A)  

Microsoft Academic Search

Objectives: Biological markers of narcolepsy with cataplexy (classical narcolepsy) include sleep-onset REM periods (SOREM) on multiple sleep latency tests (MSLT), HLA-DQB1*0602 positivity, low levels of cerebrospinal fluid (CSF) hypocretin-1 (orexin A), increased body mass index (BMI), and high levels of CSF leptin. The clinical borderland of narcolepsy and the diagnostic value of different markers of narcolepsy remain controversial and were

Claudio Bassetti; Matthias Gugger; Matthias Bischof; Johannes Mathis; Christian Sturzenegger; Esther Werth; Bogdan Radanov; Beth Ripley; Seiji Nishino; Emmanuel Mignot



Central Nervous System Toxicity and Cerebrospinal Fluid Pharmacokinetics of Intraventricularly Administered Bleomycin in Beagles1  

Microsoft Academic Search

The neurotoxic effects and cerebrospinal fluid (CSF) pharma- cokinetics of bleomycin were evaluated in beagles after chronic intraventricular administration twice a week for 8 consecutive weeks. Bleomycin was reasonably well tolerated at doses of 0.067 to 0.3 mg\\/week. Doses higher than 0.3 mg\\/week produced marked elevation of CSF protein levels and a necrotizing vas- culitis within the central nervous system.

Victor A. Levin; Deborah Byrd; Branimir I. Sikic; B. Bill Etiz; Julia Campbell; Janice K. Bereich; Richard L. Davis


Kearns-Sayre syndrome: Cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features  

Microsoft Academic Search

We evaluated cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF), biogenic amines, and white matter status in six Kearns-Sayre syndrome (KSS) patients. They presented severe 5-MTHF deficiency. A significant negative correlation was observed between CSF 5-MTHF and protein concentration. CSF homovanillic acid was clearly high. Regarding neuroimaging, the main feature was hyperintensity in the basal ganglia, brainstem, and cerebral\\/cerebellar white matter. The severity

Mercedes Serrano; María Teresa García-Silva; Elena Martin-Hernandez; Maria del Mar O’Callaghan; Pilar Quijada; Ana Martinez-Aragón; Aida Ormazábal; Alberto Blázquez; Miguel A. Martín; Paz Briones; Ester López-Gallardo; Eduardo Ruiz-Pesini; Julio Montoya; Rafael Artuch; Mercedes Pineda



Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer's disease  

Microsoft Academic Search

Cerebrospinal fluid (CSF) concentrations of tau protein were measured using an enzyme-linked immunosorbent assay which measures both normal and hyperphosphorylated tau. Levels of CSF tau were measured in 17 patients with Alzheimer's disease and 23 patients with frontotemporal dementia, and were compared to age-matched healthy controls. The CSF tau concentration in control subjects was 198±49 pg\\/ml and no relationship was

A. J. E Green; R. J Harvey; E. J Thompson; M. N Rossor



New PCR assay for rapid and quantitative detection of human cytomegalovirus in cerebrospinal fluid.  

PubMed Central

Rapid Chelex extraction combined with an automated hybridization assay for the detection of PCR-amplified human cytomegalovirus DNA from cerebrospinal fluid was established. Quantitation of DNA was performed with a plasmid being used as an external standard. The detection limit was 10 copies per microliter. Quantitative detection of human cytomegalovirus DNA could be achieved over a range from 10 to 10(4) copies per microliter.

Vogel, J U; Cinatl, J; Lux, A; Weber, B; Driesel, A J; Doerr, H W



Pediatric Neurosurgical Practice Patterns Designed to Prevent Cerebrospinal Fluid Shunt Infection  

Microsoft Academic Search

Background\\/Aims: Various factors have been associated with cerebrospinal fluid (CSF) shunt infection risk, leading to many recommendations intended to reduce that risk. We sought to assess current North American pediatric neurosurgical practice patterns in this regard via a web-based survey. Particular attention was paid to the use of antibiotic-impregnated materials and prophylactic perioperative antibiotics. Methods: The membership of the section

Thomas J. Gruber; Sara Riemer; Curtis J. Rozzelle



Proinflammatory cytokines in cerebrospinal fluid and serum in patients with disc herniation and sciatica  

Microsoft Academic Search

Proinflammatory cytokines have been identified in herniated intervertebral discs in humans, and such cytokines have experimentally been demonstrated to be important in the pathophysiological mechanisms of disc herniation. Cerebrospinal fluid (CSF) and serum concentrations of interleukin (IL)-1#, IL-6, IL-8, interferon (IFN)-% and tumour necrosis factor (TNF)-! were investigated using the enzyme-linked immunosorbent assay (ELISA) technique in 39 patients with lumbar

H. Brisby; K. Olmarker; K. Larsson; M. Nutu; B. Rydevik



Determination of haem derivatives in the cerebrospinal fluid--a semi-quantitative method.  

PubMed Central

A spectrophotometric method for semi-quantitative determination of oxyhaemoglobin, methaemoglobin and bilirubin in the cerebrospinal fluid is described and evaluated. The method involves correction for CSF protein. It is based on absorbance registrations on three wavelengths; 400, 420 and 470 nm. Reference values for a healthy control group and a hyperbilirubinaemic group are presented. Evaluation of the method shows that it is well suited to semi-quantitative determination of haem derivatives in the CSF.

Wahlgren, N G; Bergstrom, K



Plasma and cerebrospinal fluid pharmacokinetics of SU5416 after intravenous administration in nonhuman primates  

Microsoft Academic Search

Purpose: SU5416 is a small, lipophilic synthetic molecule that selectively inhibits the tyrosine kinase activity of the VEGF receptor\\u000a Flk-1\\/KDR. The role of this agent in brain tumors is currently being investigated. Pharmacokinetic studies of SU5416 have\\u000a been performed in humans; however, there have been no studies of its penetration in the cerebrospinal fluid (CSF). We studied\\u000a the pharmacokinetics of

Jamie Renbarger; Alexander Aleksic; Leticia McGuffey; Robert Dauser; Stacey Berg; Susan Blaney



Cerebrospinal fluid Tau/?-synuclein ratio in Parkinson's disease and degenerative dementias.  


Although alpha-synuclein is the main constituent of Lewy bodies, cerebrospinal fluid determination on its own does not seem fundamental for the diagnosis of synucleinopathies. We evaluated whether the combination of classical biomarkers, A?(1-42) , total tau, phosphorylated tau, and ?-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. A?(1-42) , total tau, phosphorylated tau, and ?-synuclein were measured in a series of patients with Parkinson's disease (n = 38), dementia with Lewy bodies (n = 32), Alzheimer's disease (n = 48), frontotemporal dementia (n = 31), and age-matched control patients with other neurological diseases (n = 32). Mean ?-synuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of ?-synuclein with total tau (r = -0.196, P < .01) was observed. In the group of patients with Parkinson's disease, A?(1-42) , total tau, and phosphorylated tau values were similar to controls, whereas total tau/?-synuclein and phosphorylated tau/?-synuclein ratios showed the lowest values. Cerebrospinal fluid ?-synuclein alone did not provide relevant information for Parkinson's disease diagnosis, showing low specificity (area under the curve, 0.662; sensitivity, 94%; specificity, 25%). Instead, a better performance was obtained with the total tau/?-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of ?-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/?-synuclein and phosphorylated tau/?-synuclein ratios can contribute to the discrimination of Parkinson's disease. © 2011 Movement Disorder Society. PMID:21469206

Parnetti, Lucilla; Chiasserini, Davide; Bellomo, Gianni; Giannandrea, David; De Carlo, Claudia; Qureshi, Mohamed M; Ardah, Mustafa T; Varghese, Shiji; Bonanni, Laura; Borroni, Barbara; Tambasco, Nicola; Eusebi, Paolo; Rossi, Aroldo; Onofrj, Marco; Padovani, Alessandro; Calabresi, Paolo; El-Agnaf, Omar



Bri2-23 is a potential cerebrospinal fluid biomarker in multiple sclerosis  

Microsoft Academic Search

To identify potential multiple sclerosis (MS)-specific biomarkers, we used a proteomic approach to screen cerebrospinal fluid (CSF) from 40 MS patients and 13 controls. We identified seven proteins (Beta-2-microglobulin, Bri2-23, Fetuin-A, Kallikrein-6, Plasminogen, Ribonuclease-1, and Transferrin) that had significantly altered levels in MS compared to controls. Clinical subgroup analysis revealed that decreased CSF levels of Bri2-23, a peptide cleaved from

Violaine K. Harris; Andrew Diamanduros; Pamela Good; Elina Zakin; Varun Chalivendra; Saud A. Sadiq



Infection of Cerebrospinal Fluid Shunts: Causative Pathogens, Clinical Features, and Outcomes  

Microsoft Academic Search

SUMMARY: This retrospective chart review describes the clinical features, pathogens, and outcomes of 46 patients with cerebrospinal fluid (CSF) shunt infections collected over 16 years. The overall CSF shunt infection rate was 2.1%, broken down into 1.7 and 9.3% in adult and pediatric groups, respectively. Fever and progressive consciousness disturbance were the most prominent clinical features in the adult patient

Kuo-Wei Wang; Wen-Neng Chang; Teng-Yuan Shih; Chi-Ren Huang; Nai-Wen Tsai; Chen-Sheng Chang; Yao-Chung Chuang; Po-Chou Liliang; Thung-Ming Su; Cheng-Shyuan Rau; Yu-Duan Tsai; Ben-Chung Cheng; Pi-Lien Hung; Chin-Jung Chang; Cheng-Hsien Lu


Cerebrospinal Fluid Amyloid ? 1–42 Levels in the Mild Cognitive Impairment Stage of Alzheimer's Disease  

Microsoft Academic Search

Cerebrospinal fluid (CSF) levels of amyloid ?-protein ending at amino acid position 42 (CSF-A ?1–42) and CSF-tau levels were quantified by sandwich ELISAs in 19 patients with mild cognitive impairment (MCI) who eventually developed Alzheimer's disease (AD) on follow-up as well as in 15 age-matched normal controls and 54 AD patients at diverse stages of the disease. In the present

Masahiro Maruyama; Hiroyuki Arai; Mitsunori Sugita; Haruko Tanji; Makoto Higuchi; Nobuyuki Okamura; Toshifumi Matsui; Susumu Higuchi; Sachio Matsushita; Hiroshi Yoshida; Hidetada Sasaki



The molecular forms of acetylcholinesterase in cerebrospinal fluid of normal subjects — effect of aging  

Microsoft Academic Search

Summary Acetylcholinesterase (AChE) activity is increased in human cerebrospinal fluid (CSF) during aging. The present study investigated whether the relative amounts of different molecular forms of CSF-AChE are also affected during aging. Thus, the CSF samples of healthy human subjects (age range 20–79 years, n=23) were analyzed for sedimentation forms of AChE activity. Five different forms of AChe activity were

J. Sirviii; Z. Rakonczay; P. Hartikainen; P. Kasa; P. J. Riekkinen



Intracranial Hypotension Caused by Cervical Cerebrospinal Fluid Leak: Treatment with Epidural Blood Patch  

Microsoft Academic Search

This report describes treatment with cervical epidural blood patch of low cerebrospinal fluid (CSF) pressure headache resulting from spontaneous CSF leak via a tear in a cervical dural cuff. The leak was diagnosed by a dynamic computed tomography (CT)-myelography study followed by gadolinium enhanced magnetic res- onance imaging(MRI)-scan. The epidural needle was inserted with the aid of image intensifier and

Michael J. Cousins; David Brazier; Raymond Cook



5-Hydroxyindoleacetic Acid Levels in the Cerebrospinal Fluid of Depressive Patients treated with Probenecid  

Microsoft Academic Search

ACCORDING to the serotonin (5-hydroxytryptamine, 5-HT) hypothesis there is a causal relationship between mental depression and 5-HT deficiency in the brain1-3. Some depressive patients-mainly those suffering from an endogenous depression-display the following clinical signs. (1) The concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) (refs. 4 and 5) and the urinary concentrations of 5-HT (ref. 6) and 5-HIAA

H. M. van Praag; J. Korf; J. Puite



Polyclonal B-Cell Expansion in the Cerebrospinal Fluid of Patients with Psedotumor Cerebri  

Microsoft Academic Search

To investigate the hypothesis that pseudotumor cerebri (PTC) is associated with humoral immunity, we analyzed immunoglobulin heavy chain variable region (Ig-VH) genes of B cells in the cerebrospinal fluid (CSF) of 10 patients with PTC. Using RT-PCR and sequencing techniques, intrathecal B-cell Ig-VH genes were amplified in 6 of 10 PTC samples. Sequence analysis of complementarity-determining region 3 (CDR 3)




Cerebrospinal fluid (CSF) and serum S100B: release and wash-out pattern  

Microsoft Academic Search

S100B is an important brain specific protein for monitoring damage and activation of astrocytes. Using a straight forward, non-resource demanding in-house ELISA technique we measured S100B in cerebrospinal fluid (CSF) and serum in patients with traumatic brain injury (TBI) (serum), subarachnoid hemorrhage (SAH) (CSF, serum), intracranial hemorrhage (ICH) (CSF, serum), normal controls (NC) (serum) and a reference population (CSF, N=409).

A. Petzold; G. Keir; D. Lim; M. Smith; E. J. Thompson



Treatment of Cerebrospinal Fluid Shunting Complications in a Nigerian Neurosurgery Programme  

Microsoft Academic Search

Background\\/Aims: For a century since the first cerebrospinal fluid (CSF) shunt surgery, ventriculoperitoneal (VP) shunt insertion for the treatment of hydrocephalus has routinely been performed. A lot of common and rare complications following this procedure have been reported in 24–47% of the cases. The aim of this paper was to present our experience with the treatment of hydrocephalus in our

Edward O. Komolafe; Augustine A. Adeolu; Morenikeji A. Komolafe



S-100 protein concentration in the cerebrospinal fluid of patients with Creutzfeldt-Jakob disease  

Microsoft Academic Search

We evaluated S-100 levels in paired cerebrospinal fluid (CSF) and serum samples in a group of 135 patients referred to the\\u000a German Creutzfeldt-Jakob disease (CJD) surveillance unit from June 1993 to May 1995. The patients were seen in a prospective\\u000a case control study. The diagnosis of probable CJD during life was made in any patient presenting with rapidly progressive\\u000a dementia

Markus Otto; Holger Stein; Annemarie Szudra; Inga Zerr; Monika Bodemer; Olaf Gefeller; Sigrid Poser; Hans A. Kretzschmar; Michael Mäder; Thomas Weber



Spontaneous Pneumocephalus Caused by Pneumococcal Meningitis  

PubMed Central

Pneumocephalus is a condition characterized by the presence of air in the cranium, and it is mainly caused by trauma or a neurosurgical procedure. In the absence of head trauma or a neurosurgical procedure, meningitis is an extremely rare cause of pneumocephalus. Here, the authors present a rare case of spontaneous pneumocephalus caused by pneumococcal meningitis, in which simple lateral radiography and computed tomography (CT) findings of the skull suggested the diagnosis. Cerebrospinal fluid analysis showed bacterial meningitis which later revealed streptococcus pneumonia. The patient was treated with antibiotics and responded remarkably well. Repeat CT performed after 2 weeks of treatment showed complete resolution of the intracranial gas. Here, the authors report an unusual case of a pneumocephalus caused by meningitis in the absence of head trauma or a neurosurgical procedure.

Kim, Hyun Sook; Kim, Sung Hoon



Quantification of poly(ADP-ribose)-modified proteins in cerebrospinal fluid from infants and children after traumatic brain injury  

Microsoft Academic Search

Poly-ADP-ribosylation (PAR) of proteins by poly(ADP-ribose) polymerases (PARP) occurs after experimental traumatic brain injury (TBI) and modulates neurologic outcome. Several promising pharmacological PARP inhibitors have been developed for use in humans, but there is currently no clinically relevant means of monitoring treatment effects. We therefore used an enzyme-linked immunosorbent assay to measure PAR-modified proteins in cerebrospinal fluid (CSF). Cerebrospinal fluid

Ericka L Fink; Yichen Lai; Xiaopeng Zhang; Keri Janesko-Feldman; P David Adelson; Csaba Szabó; Rachel P Berger; Ajit A Sarnaik; Patrick M Kochanek; Robert S B Clark; RSB Clark



Peripheral neuroactive steroids may be as good as the steroids in the cerebrospinal fluid for the diagnostics of CNS disturbances  

Microsoft Academic Search

To compare the predictivity of the neuroactive steroids in the cerebrospinal fluid and peripheral blood for the diagnostics of CNS disturbances, eighteen unconjugated steroids were quantified in the cerebrospinal fluid (CSF) from the 3rd ventricle and 18 unconjugated steroids and 7 steroid polar conjugates were measured in the serum using GC–MS and RIA. Eight postmenopausal women (56–78 years of age)

Radmila Kancheva; Martin Hill; Zden?k Novák; Jan Chrastina; Marta Velíková; Lyudmila Kancheva; Ivo ?íha; Luboslav Stárka



Development of a theoretical framework for analyzing cerebrospinal fluid dynamics  

PubMed Central

Background To date hydrocephalus researchers acknowledge the need for rigorous but utilitarian fluid mechanics understanding and methodologies in studying normal and hydrocephalic intracranial dynamics. Pressure volume models and electric circuit analogs introduced pressure into volume conservation; but control volume analysis enforces independent conditions on pressure and volume. Previously, utilization of clinical measurements has been limited to understanding of the relative amplitude and timing of flow, volume and pressure waveforms; qualitative approaches without a clear framework for meaningful quantitative comparison. Methods Control volume analysis is presented to introduce the reader to the theoretical background of this foundational fluid mechanics technique for application to general control volumes. This approach is able to directly incorporate the diverse measurements obtained by clinicians to better elucidate intracranial dynamics and progression to disorder. Results Several examples of meaningful intracranial control volumes and the particular measurement sets needed for the analysis are discussed. Conclusion Control volume analysis provides a framework to guide the type and location of measurements and also a way to interpret the resulting data within a fundamental fluid physics analysis.

Cohen, Benjamin; Voorhees, Abram; Vedel, S?ren; Wei, Timothy



Radioimmunoassay of serotonin (5-hydroxytryptamine) in cerebrospinal fluid, plasma, and serum  

SciTech Connect

A direct radioimmunoassay is described for serotonin (5-hydroxytryptamine) in cerebrospinal fluid, platelet-poor plasma, and serum. Antisera in rabbits was raised against serotonin diazotized to a conjugate of bovine albumin and D,L-p-aminophenylalanine. Polyethylene glycol, alone or in combination with anti-rabbit immunoglobulins, is used to separate bound and unbound tritiated serotonin. The minimum concentration of serotonin detectable is 2 nmol/L in a sample. Within-day precision (CV) is 4.3% between-day precision 7.7%. Analytical recoveries of serotonin are 109% and 101% for cerebrospinal fluid and plasma, respectively. Tryptophan, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol do not interfere with the assay. However, 5-methoxytryptamine and tryptamine cross react. Of samples of cerebrospinal fluid from patients with disc herniations (n=21) or low-pressure hydrocephalus (n=10), one-third had concentrations of 2-4 nmol/L and two-thirds were below the minimum detectable concentration. The observed range for the concentration of serotonin in plasma of 14 normal subjects was 5-14 nmol/L (mean +/- SD, 9 +/- 3 nmol/L). The observed ranges for serotonin in serum were: for 10 women 520-900 (mean +/- SD: 695 +/- 110) nmol/L and for 10 men 380-680 (520 +/- 94) nmol/L.

Engbaek, F.; Voldby, B



Cerebrospinal Fluid and Blood Biomarkers of Neuroaxonal Damage in Multiple Sclerosis  

PubMed Central

Following emerging evidence that neurodegenerative processes in multiple sclerosis (MS) are present from its early stages, an intensive scientific interest has been directed to biomarkers of neuro-axonal damage in body fluids of MS patients. Recent research has introduced new candidate biomarkers but also elucidated pathogenetic and clinical relevance of the well-known ones. This paper reviews the existing data on blood and cerebrospinal fluid biomarkers of neuroaxonal damage in MS and highlights their relation to clinical parameters, as well as their potential predictive value to estimate future disease course, disability, and treatment response. Strategies for future research in this field are suggested.

Dujmovic, Irena



Application of Control Volume Analysis to Cerebrospinal Fluid Dynamics  

NASA Astrophysics Data System (ADS)

Hydrocephalus is among the most common birth defects and may not be prevented nor cured. Afflicted individuals face serious issues, which at present are too complicated and not well enough understood to treat via systematic therapies. This talk outlines the framework and application of a control volume methodology to clinical Phase Contrast MRI data. Specifically, integral control volume analysis utilizes a fundamental, fluid dynamics methodology to quantify intracranial dynamics within a precise, direct, and physically meaningful framework. A chronically shunted, hydrocephalic patient in need of a revision procedure was used as an in vivo case study. Magnetic resonance velocity measurements within the patient's aqueduct were obtained in four biomedical state and were analyzed using the methods presented in this dissertation. Pressure force estimates were obtained, showing distinct differences in amplitude, phase, and waveform shape for different intracranial states within the same individual. Thoughts on the physiological and diagnostic research and development implications/opportunities will be presented.

Wei, Timothy; Cohen, Benjamin; Anor, Tomer; Madsen, Joseph



Effect of cerebral injury on cerebrospinal fluid cyclic AMP concentration.  


Cerbrospinal fluid (CSF) cyclic adenosine-3', 5'-monophosphate (cAMP) was measured in rabbits after experimental brain injury as well as in patients with cerebral contusion and cerebral concussion. In rabbits a marked elevation lasting for two weeks was observed. From the third week onwards after the injury the CSF cAMP concentration was lower than the basal level before the injury. Dexamethasone partly inhibited the elevation. Ethanol treatment decreased the CSF cAMP values. In man, the CSF cAMP concentration was significantly higher in patients with cerebral contusion than in those with cerebral concussion. Also in the latter group the cAMP values were higher than in control patients. Due to the clear differences between the various groups, measurement of cAMP concentration in CSF might have diagnostic value in evaluation of the severity of cerebral lesion in the acute phase. Also the activities of some enzymes were measured, and the results were parallel with cAMP changes but less striking. PMID:186266

Myllyla, V V



Cerebrospinal fluid (CSF) transient responses induced by hypercapnia  

SciTech Connect

CSF transient responses to CO/sub 2/ inhalation were measured before and after facilitated perfusate flow through subarachnoid spaces of anesthetized cats during ventriculocisternal perfusion with artificial CSF containing /sup 14/C-dextran. Convective mixing of perfusate in subarachnoid spaces was augmented while infusion constant, either by impeding cisternal efflux of perfusate by raising the cisternal outflow cannula (high CSF pressure), or by preventing CSF outflow by clamping the cisternal outflow cannula (stopflow; S-F). CSF transients were also measured before and after systemic administration of phenoxybenzamine (PBZ) in order to evaluate the contribution of sympatho-adrenergic activity to craniospinal CSF redistribution and mixing. Results from high CSF pressure and S-F experiments indicate that unequilibrated CSF contributes significantly to the reduced tracer concentration in CSF volume (Vd) since SCF effluent tracer concentration (Cd) was decreased after subarachnoid facilitated flow. Further, results from S-F studies indicate that at least 50% of Cd is due to craniospinal fluid redistribution, a process which, along with CSF outflow transients, was unaffected by PBZ. Conversely, PBZ administration decreased steady state SCF formation and absorption through alpha-mediated cerebrovascular responses and/or through beta-adrenoceptor inhibition of metabolism of CSF secretory epithelium.

Fisher, M.J.



Cerebrospinal fluid flow imaging by using phase-contrast MR technique  

PubMed Central

Cerebrospinal fluid (CSF) spaces include ventricles and cerebral and spinal subarachnoid spaces. CSF motion is a combined effect of CSF production rate and superimposed cardiac pulsations. Knowledge of CSF dynamics has benefited considerably from the development of phase-contrast (PC) MRI. There are several disorders such as communicating and non-communicating hydrocephalus, Chiari malformation, syringomyelic cyst and arachnoid cyst that can change the CSF dynamics. The aims of this pictorial review are to outline the PC MRI technique, CSF physiology and cerebrospinal space anatomy, to describe a group of congenital and acquired disorders that can alter the CSF dynamics, and to assess the use of PC MRI in the assessment of various central nervous system abnormalities.

Battal, B; Kocaoglu, M; Bulakbasi, N; Husmen, G; Tuba Sanal, H; Tayfun, C



Salmonella enterica Serotype Arizonae Meningitis in a Neonate  

PubMed Central

Typhoidal and nontyphoidal salmonella infections are common causes of gastroenteritis in the community. However, salmonella only rarely causes invasive infections like meningitis. We report a 13-day-old female neonate with signs and symptoms of meningitis whose cerebrospinal fluid (CSF) culture showed Salmonella enterica serotype Arizonae that was sensitive to ceftriaxone. She presented with fever and failure to feed for 2 days. Despite prompt treatment with ampicillin, gentamicin, and ceftriaxone, she developed communicating hydrocephalus, frequent seizures, and coma that progressed to death after 2 weeks of hospitalization. Salmonella enterica serotype Arizonae is a rare cause of human infection known to leading to meningitis symptoms similar to those caused by other salmonella species. This is the first report of it as a cause of meningitis in a child under one month of age. Therefore, it should be included in the differential diagnosis of Gram-negative bacillary meningitis in immunocompromised children, neonates, and those with contacts with reptiles.

Lakew, Wubishet; Girma, Abayneh; Triche, Elizabeth



Transmigration of polymorphnuclear neutrophils and monocytes through the human blood-cerebrospinal fluid barrier after bacterial infection in vitro  

PubMed Central

Background Bacterial invasion through the blood-cerebrospinal fluid barrier (BCSFB) during bacterial meningitis causes secretion of proinflammatory cytokines/chemokines followed by the recruitment of leukocytes into the CNS. In this study, we analyzed the cellular and molecular mechanisms of polymorphonuclear neutrophil (PMN) and monocyte transepithelial transmigration (TM) across the BCSFB after bacterial infection. Methods Using an inverted transwell filter system of human choroid plexus papilloma cells (HIBCPP), we studied leukocyte TM rates, the migration route by immunofluorescence, transmission electron microscopy and focused ion beam/scanning electron microscopy, the secretion of cytokines/chemokines by cytokine bead array and posttranslational modification of the signal regulatory protein (SIRP) ? via western blot. Results PMNs showed a significantly increased TM across HIBCPP after infection with wild-type Neisseria meningitidis (MC58). In contrast, a significantly decreased monocyte transmigration rate after bacterial infection of HIBCPP could be observed. Interestingly, in co-culture experiments with PMNs and monocytes, TM of monocytes was significantly enhanced. Analysis of paracellular permeability and transepithelial electrical resistance confirmed an intact barrier function during leukocyte TM. With the help of the different imaging techniques we could provide evidence for para- as well as for transcellular migrating leukocytes. Further analysis of secreted cytokines/chemokines showed a distinct pattern after stimulation and transmigration of PMNs and monocytes. Moreover, the transmembrane glycoprotein SIRP? was deglycosylated in monocytes, but not in PMNs, after bacterial infection. Conclusions Our findings demonstrate that PMNs and monoctyes differentially migrate in a human BCSFB model after bacterial infection. Cytokines and chemokines as well as transmembrane proteins such as SIRP? may be involved in this process.



Laboratory diagnosis of bacterial meningitis.  

PubMed Central

Bacterial meningitis is relatively common, can progress rapidly, and can result in death or permanent debilitation. This infection justifiably elicits strong emotional reactions and, hopefully, immediate medical intervention. This review is a brief presentation of the pathogenesis of bacterial meningitis and a review of current knowledge, literature, and recommendations on the subject of laboratory diagnosis of bacterial meningitis. Those who work in clinical microbiology laboratories should be familiar with the tests used in detecting bacteria and bacterial antigens in cerebrospinal fluid (CSF) and should always have the utmost appreciation for the fact that results of such tests must always be reported immediately. Academic and practical aspects of the laboratory diagnosis of bacterial meningitis presented in this review include the following: anatomy of the meninges; pathogenesis; changes in the composition of CSF; etiological agents; processing CSF; microscopic examination of CSF; culturing CSF; methods of detecting bacterial antigens and bacterial components in CSF (counter-immunoelectrophoresis, coagglutination, latex agglutination, enzyme-linked immunosorbent assay, Limulus amebocyte lysate assay, and gas-liquid chromatography); use of the polymerase chain reaction; and practical considerations for testing CSF for bacterial antigens.

Gray, L D; Fedorko, D P



Clearance from cerebrospinal fluid of intrathecally administered beta-endorphin in monkeys  

SciTech Connect

Five adult male monkeys (Macaca mulatta) weighing 7.1-9.9 kg were given synthetic human beta-endorphin (800 micrograms) and (/sup 14/C)methoxy-inulin (50 microCi) in 400 microliters of normal saline intrathecally. Serial samples of cerebrospinal fluid were drawn through a previously positioned indwelling spinal catheter and were assayed for concentrations of beta-endorphin (determined by radioimmunoassay) and inulin (determined by liquid scintillation counter). Spinal fluid concentrations of beta-endorphin and inulin peaked and declined in a parallel manner. The clearance ratio (calculated from the reciprocal of the ratio of the areas under the respective curves of elimination of the two species) remained remarkably similar from animal to animal, giving a mean value of 1.060 +/- 0.090 (SEM). This ratio, being near unity, suggests that beta-endorphin is eliminated from spinal fluid in a fashion similar to that of inulin, which is removed exclusively by bulk absorption.

Lee, V.C.; Burns, R.S.; Dubois, M.; Cohen, M.R.



Distal Aortic Perfusion and Cerebrospinal Fluid Drainage for Thoracoabdominal and Descending Thoracic Aortic Repair  

PubMed Central

Objective: To report the long-term results of our experience using cerebrospinal fluid drainage and distal aortic perfusion in descending thoracic and thoracoabdominal aortic repair. Summary Background Data: Repair of thoracoabdominal and thoracic aortic aneurysm by the traditional clamp-and-go technique results in a massive ischemic insult to several major organ systems. Ten years ago, we began to use distal aortic perfusion and cerebrospinal fluid drainage (adjunct) to reduce end-organ ischemia. Methods: Between January 1991 and February 2003, we performed 1004 thoracoabdominal or descending thoracic repairs. Adjunct was used in 741 (74%) of 1004. Multivariable data were analyzed by Cox regression. Number needed to treat was calculated as the reciprocal of the risk difference. Results: Immediate neurologic deficit was 18 (2.4%) of 741 with adjunct and 18 (6.8%) of 263 without (P < 0.0009). In high-risk extent II aneurysms, the numbers were 11 (6.6%) of 167 with adjunct, and 11 (29%) of 38 without. Long-term survival was improved with adjunct (P < 0.002). The long-term survival results persisted after adjustment for age, extent II aneurysm, and preoperative renal function. Conclusion: Use of adjunct over a long period of time has produced favorable results; approximately 1 neurologic deficit saved for every 20 uses of adjunct overall. In extent II aneurysms, where the effect is greatest, this increases to 1 saved per 5 uses. Adjunct is also associated with long-term survival, which is consistent with mitigation of ischemic end-organ injury. These long-term results indicate that cerebrospinal fluid drainage and distal aortic perfusion are safe and effective adjunct for reducing morbidity and mortality following thoracic and thoracoabdominal aortic repair.

Safi, Hazim J.; Miller, Charles C.; Huynh, Tam T.T.; Estrera, Anthony L.; Porat, Eyal E.; Winnerkvist, Anders N.; Allen, Bradley S.; Hassoun, Heitham T.; Moore, Frederick A.



Trace and major elements in whole blood, serum, cerebrospinal fluid and urine of patients with Parkinson’s disease  

Microsoft Academic Search

Summary. Quantifications of Al, Ca, Cu, Fe, Mg, Mn, Si and Zn were performed in urine, serum, blood and cerebrospinal fluid (CSF) of 26 patients affected by Parkinson’s disease (PD) and 13 age-matched controls to ascertain the potential role of biological fluids as markers for this pathology. Analyses were performed by Inductively Coupled Plasma Atomic Emission Spectrometry and Sector Field

G. Forte; B. Bocca; O. Senofonte; F. Petrucci; L. Brusa; P. Stanzione; S. Zannino; N. Violante; A. Alimonti; G. Sancesario



Cerebrospinal fluid concentrations of nitrate plus nitrite during the treatment of acute lymphoblastic leukaemia in childhood.  


To investigate the hypothesis that acute lymphoblastic leukaemia (ALL) and its treatment disturb central nervous system nitric oxide metabolism, 11 patients were studied. Serial cerebrospinal fluid (CSF) samples were collected throughout treatment and the concentration of nitrate plus nitrite (NOx) was measured. Compared to an age-matched reference population, CSF NOx was significantly increased before treatment and rose further during the induction phase of treatment. Concentrations remained high during consolidation treatment, but fell during continuing treatment and normalised by the end of treatment. In conclusion, ALL and its treatment cause an increase in central nervous system nitric oxide production. reserved. PMID:9680103

Surtees, R; Clelland, J; Heales, S



Non Invasive Microwave Sensor for the Detection of Lactic Acid in Cerebrospinal Fluid (CSF)  

NASA Astrophysics Data System (ADS)

This research involves the use of a low power microwave sensor for analysis of lactic acid in cerebrospinal fluid (CSF), an indicator of neurological impairment during aortic aneurysm surgery which could provide the basis for improved treatment regimes and better quality of care with more efficient use of resources. This paper presents initial work using standard lactate curves in water followed by lactate in "synthetic CSF". A multi-modal spectral signature has been defined for lactate, forming the basis for subsequent development of microwave sensor platform that is able to detect concentrations of lactic acid in CSF of volumes less than 1ml.

Goh, J. H.; Mason, A.; Al-Shamma'a, A. I.; Field, M.; Shackcloth, M.; Browning, P.



Evaluation of apoptosis in cerebrospinal fluid of patients with severe head injury  

Microsoft Academic Search

Summary  \\u000a Objective. To determine whether sFas, caspase-3, proteins which propagate apoptosis, and bcl-2, a protein which inhibits apoptosis, would be increased in cerebrospinal fluid (CSF) in patients with severe traumatic brain\\u000a injury (TBI) and to examine the correlation of sFas, caspase-3, and bcl-2 with each other and with clinical variables.\\u000a \\u000a \\u000a Methods. sFas, caspase-3, and bcl-2 were measured in CSF of

M. Uzan; H. Erman; T. Tanriverdi; G. Z. Sanus; A. Kafadar; H. Uzun



A tomographic study of the skull base in primary spontaneous cerebrospinal fluid leaks  

Microsoft Academic Search

Introduction  This study aims to evaluate the existence of anatomic abnormalities in the skull base that could contribute to the origin\\u000a of primary spontaneous cerebrospinal fluid leaks (PSL).\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Twenty PSL patients were compared with 20 healthy individuals. The following features were measured through an analysis of\\u000a computed tomography scans: the angles of the petrosal bones and skull base in both the

Alexandre Varella Giannetti; Roberto Eustáquio S. Guimarães; Ana Paula M. S. Santiago; Francisco Otaviano L. Perpétuo; Marco Antônio O. Machado


Identification of Sarcocystis capracanis in cerebrospinal fluid from sheep with neurological disease.  


Protozoal merozoites were identified in the cerebrospinal fluid of two sheep with neurological disease in the UK. Polymerase chain reaction (PCR) identified the merozoites as Sarcocystis capracanis, a common protozoal pathogen of goats. This is the first report of this species infecting sheep and may represent an aberrant infection with sheep acting as dead end hosts, or alternatively could indicate that sheep are able to act as intermediate hosts for S. capracanis, widening the previously reported host range of this pathogen. It is possible that S. capracanis is a previously unrecognised cause of ovine protozoal meningoencephalitis (OPM) in the UK. PMID:23312871

Formisano, P; Aldridge, B; Alony, Y; Beekhuis, L; Davies, E; Del Pozo, J; Dunn, K; English, K; Morrison, L; Sargison, N; Seguino, A; Summers, B A; Wilson, D; Milne, E; Beard, P M



Cranial computerized tomography and cerebrospinal fluid procoagulant activity in childhood acute lymphoblastic leukemia.  


Thirty-three children with acute lymphoblastic leukemia (ALL) were studied using serial cranial computerized tomography (CCT) and cerebrospinal fluid procoagulant activity (PCA) for 5 years from the time of diagnosis. PCA was also studied in control children without neurological disease and in those with a variety of neurological disorders. Temporary elevation in the CSF PCA was observed during the phase of prophylactic central nervous system treatment in ALL and there was a late rise at 2-3 years off treatment. PCA also rose in the CSF following CNS disturbance in neurologically abnormal children, which suggests that the elevation observed in ALL is not specific to myelin disturbance. PMID:3152956

O'Hare, A E; Eden, O B; Simpson, R M; Donaldson, A; Sainsbury, C P



Cerebrospinal fluid protein changes in multiple sclerosis after dental amalgam removal.  


A relationship between multiple sclerosis (MS) and dental silver-mercury fillings has been suggested by some investigators, but never proven. This study documents objective biochemical changes following the removal of these fillings along with other dental materials, utilizing a new health care model of multidisciplinary planning and treatment. The dramatic changes in photolabeling of cerebrospinal fluid (CSF) proteins following these dental interventions suggest CSF photolabeling may serve as an objective biomarker for monitoring MS. The clear-cut character of these changes should also encourage more research to better define this possible association between dental mercury and MS. PMID:9727079

Huggins, H A; Levy, T E



Decreased Lithium Disposition to Cerebrospinal Fluid in Rats with Glycerol-induced Acute Renal Failure  

Microsoft Academic Search

Purpose  The lithium disposition to cerebrospinal fluid (CSF) was evaluated in rats with acute renal failure (ARF) to examine whether\\u000a electrolyte homeostasis of the CSF is perturbed by kidney dysfunction. In addition, the effects of renal failure on choroid\\u000a plexial expressions of the Na+–K+–2Cl? co-transporter (NKCC1) and Na+\\/H+ exchanger (NHE1) were also studied.\\u000a \\u000a \\u000a \\u000a Methods  After lithium was intravenously administered at a dose

Rie Sakae; Atsuko Ishikawa; Tomoko Niso; Yukiko Komori; Tetsuya Aiba; Hiromu Kawasaki; Yuji Kurosaki



Hepatic cerebrospinal fluid pseudocyst mimicking hydatid liver disease: a case report  

PubMed Central

Introduction An abdominal pseudocyst is a rare complication of a ventriculo-peritoneal shunt. Etiological factors include infection, obstruction and dislodgement. This is the first report of a hepatic cerebrospinal fluid pseudocyst mimicking hydatid liver disease. Case presentation We report the case of an 18-year-old Caucasian male patient who presented with a hepatic pseudocyst secondary to a ventriculo-peritoneal shunt, misdiagnosed as hydatid disease of the liver. Conclusion Hepatic pseudocysts, a rare complication of a ventriculo-peritoneal shunt, have similar clinical and radiological characteristics to those of hydatid liver disease. The formation of a pseudocyst should always be considered in patients with ventriculo-peritoneal shunts in situ.



Hearing loss and cerebrospinal fluid pressure: case report and review of the literature.  


A decrease in cerebrospinal fluid pressure may result in an endolymphatic hydrops through a patent cochlear aqueduct or through the fundus of the internal auditory canal. This hydrops typically leads to low-frequency sensorineural hearing loss. We describe the case of a man who presented with a subjective and objective hearing loss in addition to a headache 4 days after he had undergone a dural puncture. We treated him with a standard epidural blood patch. Immediately after treatment, his hearing improved and his headache resolved. PMID:18404909

Pogodzinski, Matthew S; Shallop, Jon K; Sprung, Juraj; Weingarten, Toby N; Wong, Gilbert Y; McDonald, Thomas J



Kearns-Sayre syndrome: cerebral folate deficiency, MRI findings and new cerebrospinal fluid biochemical features.  


We evaluated cerebrospinal fluid (CSF) 5-methyltetrahydrofolate (5-MTHF), biogenic amines, and white matter status in six Kearns-Sayre syndrome (KSS) patients. They presented severe 5-MTHF deficiency. A significant negative correlation was observed between CSF 5-MTHF and protein concentration. CSF homovanillic acid was clearly high. Regarding neuroimaging, the main feature was hyperintensity in the basal ganglia, brainstem, and cerebral/cerebellar white matter. The severity of hemispheric white matter disturbances appeared to be qualitatively associated with 5-MTHF values. The negative correlation between 5-MTHF and proteins supports the hypothesis of impaired choroid plexus function. Interestingly, despite very low 5-MTHF, clearly high neurotransmitter metabolites were found. PMID:20388557

Serrano, Mercedes; García-Silva, María Teresa; Martin-Hernandez, Elena; O'Callaghan, Maria del Mar; Quijada, Pilar; Martinez-Aragón, Ana; Ormazábal, Aida; Blázquez, Alberto; Martín, Miguel A; Briones, Paz; López-Gallardo, Ester; Ruiz-Pesini, Eduardo; Montoya, Julio; Artuch, Rafael; Pineda, Mercedes



Longitudinal assessment of tau and amyloid beta in cerebrospinal fluid of Parkinson disease.  


Tau gene has been consistently associated with the risk of Parkinson disease in recent genome wide association studies. In addition, alterations of the levels of total tau, phosphorylated tau [181P], and amyloid beta 1-42 in cerebrospinal fluid have been reported in patients with sporadic Parkinson disease and asymptomatic carriers of leucine-rich repeat kinase 2 mutations, in patterns that clearly differ from those typically described for patients with Alzheimer disease. To further determine the potential roles of these molecules in Parkinson disease pathogenesis and/or in tracking the disease progression, especially at early stages, the current study assessed all three proteins in 403 Parkinson disease patients enrolled in the DATATOP (Deprenyl and tocopherol antioxidative therapy of parkinsonism) placebo-controlled clinical trial, the largest cohort to date with cerebrospinal fluid samples collected longitudinally. These initially drug-naive patients at early disease stages were clinically evaluated, and cerebrospinal fluid was collected at baseline and then at endpoint, defined as the time at which symptomatic anti-Parkinson disease medications were determined to be required. General linear models were used to test for associations between baseline cerebrospinal fluid biomarker levels or their rates of change and changes in the Unified Parkinson Disease Rating Scale (total or part III motor score) over time. Robust associations among candidate markers are readily noted. Baseline levels of amyloid beta were weakly but negatively correlated with baseline Unified Parkinson Disease Rating Scale total scores. Baseline phosphorylated tau/total tau and phosphorylated tau/amyloid beta were significantly and negatively correlated with the rates of the Unified Parkinson Disease Rating Scale change. While medications (deprenyl and/or tocopherol) did not appear to alter biomarkers appreciably, a weak but significant positive correlation between the rate of change in total tau or total tau/amyloid beta levels and the change of the Unified Parkinson Disease Rating Scale was observed. Notably, these correlations did not appear to be influenced by APOE genotype. These results are one of the very first pieces of evidence suggesting that tau and amyloid beta are critically involved in early Parkinson disease progression, potentially by a different mechanism than that in Alzheimer disease, although their applications as Parkinson disease progression markers will likely require the addition of other proteins. PMID:23644819

Zhang, Jing; Mattison, Hayley A; Liu, Changqin; Ginghina, Carmen; Auinger, Peggy; McDermott, Michael P; Stewart, Tessandra; Kang, Un Jung; Cain, Kevin C; Shi, Min



Maraviroc-containing regimen suppresses HIV replication in the cerebrospinal fluid of patients with neurological symptoms.  


We report the concentrations of maraviroc in the cerebrospinal fluid (CSF) and plasma of six HIV-1-infected patients with both neurological impairment and detectable HIV-1 replication in CSF. One month after starting maraviroc, the viral load in the CSF decreased significantly (P = 0.005). The median (range) maraviroc concentration in plasma was 347 ng/ml (123-2678). Four patients had CSF concentrations above the protein-adjusted inhibitory concentration (IC90) of 0.57 ng/ml (0.06-10.7) with a median of 102 ng/ml (35-173). PMID:20601852

Melica, Giovanna; Canestri, Ana; Peytavin, Gilles; Lelievre, Jean D; Bouvier-Alias, Magali; Clavel, Cyril; Calvez, Vincent; Lascaux, Anne S; Katlama, Christine; Levy, Yves



The role of cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis. where are we now?  


Alzheimer's disease (AD) is a rapidly growing disease that is estimated to affect about 36 million people worldwide, therefore there is an immediate need for its' early diagnosis and treatment. A number of research studies are performed on possible accurate and reliable diagnostic biomarkers of AD. This review study provides an update on the cerebrospinal fluid (CSF) proteins that are being currently used in clinical practice and studied as biomarkers for early AD diagnosis and their future prospects, as well as relevant patents. PMID:23489287

Papaliagkas, Vasileios T



Non-linear relationships of cerebrospinal fluid biomarker levels with cognitive function: an observational study  

Microsoft Academic Search

Introduction  Levels of cerebrospinal fluid (CSF) ?-amyloid (A?) and Tau proteins change in Alzheimer's disease (AD). We tested if the relationships\\u000a of these biomarkers with cognitive impairment are linear or non-linear.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  We assessed cognitive function and assayed CSF A? and Tau biomarkers in 95 non-demented volunteers and 97 AD patients. We\\u000a then tested non-linearities in their inter-relations.\\u000a \\u000a \\u000a \\u000a \\u000a Results  CSF biomarkers related to

Jonathan H Williams; Gordon K Wilcock; Jeffrey Seeburger; Aimee Dallob; Omar Laterza; William Potter; A David Smith



Linezolid for treatment of catheter-related cerebrospinal fluid infections in preterm infants.  


Ventriculostomy-related cerebrospinal fluid (CSF) infection remains a major problem in neonatal intensive care. The spectrum of pathogens causing these infections is dominated by coagulase-negative staphylococci, and vancomycin is the antibiotic of choice for treatment. However, vancomycin is known to have only poor penetration into the CSF when applied intravenously and is therefore being applied intraventricularly. The oxazolidinone linezolid has antibacterial activity against most drug-resistant Gram-positive bacteria and has been shown to have excellent penetration into the CSF in adults. Here, its successful use in five neonates with infected ventriculostomies is described. PMID:21686411

Langgartner, M; Mutenthaler, A; Haiden, N; Pollak, A; Berger, A



A case of systemic lupus erythematosus presenting transverse myelitis after an episode of meningitis  

Microsoft Academic Search

A 27-year-old woman suffering from systemic lupus erythematosus was admitted because she had motor and sensory palsy of the lower extremities, neck stiffness, and a fever. Cerebrospinal fluid study indicated meningitis, and magnetic resonance imaging revealed cord swelling and high signals at Th9–Th12 levels. Antibiotics treatment led to resolution of the meningeal signs. Intravenous cyclophosphamide and prednisolone resulted in a

Toru Yago; Mutsuto Tateishi; Naomi Ichikawa; Takefumi Furuya; Tadashi Sakurai; Hiroshi Nakajima; Masako Hara; Naoyuki Kamatani



Multiple Therapeutic Effects of Adjunctive Baicalin Therapy in Experimental Bacterial Meningitis  

Microsoft Academic Search

\\u000a Abstract\\u000a   This study aimed to examine effects of adjunctive baicalin therapy to ampicillin for experimental bacterial meningitis in\\u000a rabbits. After Escherichia Coli inoculation, mean leukocyte counts, concentrations of protein, tumor necrosis factor-? (TNF-?), interleukin-1 (IL-1) and\\u000a lactate in cerebrospinal fluid (CSF), brain water content and mean arterial and intracranial pressures substantially increased\\u000a in the meningitis group. Ampicillin alone for 5 h

Yong-Jun Tang; Fu-Wen Zhou; Zi-Qiang Luo; Xin-Zhong Li; Hui-Ming Yan; Ming-Jie Wang; Fu-Rong Huang; Shao-Jie Yue



Fluconazole treatment of Blastoschizomyces capitatus meningitis in an allogeneic bone marrow recipient  

Microsoft Academic Search

The first known case ofBlastoschizomyces capitatus meningitis occurring in an allogeneic bone marrow recipient on steroid and cyclosporine therapy for chronic graft-versus-host disease is reported. An 11-month course of treatment with oral fluconazole resulted in resolution of the meningeal syndrome and eradication ofBlastoschizomyces capitatus from the cerebrospinal fluid. Three months after discontinuation of fluconazole the patient died due to idiopathic

C. Girmenia; A. Micozzi; M. Venditti; G. Meloni; A. P. Iori; S. Bastianello; P. Martino



N-acetylaspartic acid (NAA) and N-acetylaspartylglutamic acid (NAAG) in human ventricular, subarachnoid, and lumbar cerebrospinal fluid.  


N-Acetylaspartic and N-acetylaspartylglutamic acid concentrations in human ventricular, subarachnoid and lumbar cerebrospinal fluid were measured by combined gas chromatography-mass spectrometry using selected ion monitoring with deuterated internal standards. N-Acetylaspartate concentrations were in the range 55, 9, and 1 microM, respectively; N-acetylaspartylglutamate concentrations in the same fluids were in the range 8, 3 and 4 microM, respectively. There did not appear to be any difference in lumbar fluid concentrations of either compound between control subjects, schizophrenic patients, Alzheimer's disease patients and a pooled group of patients with neurological degeneration. Ventricular concentrations of both compounds were greatly increased in deceased patients suggesting that maintenance of their intracellular concentrations is probably energy dependent. The concentrations of these compounds in lumbar cerebrospinal fluid from living, and ventricular cerebrospinal fluid from deceased subjects were weakly correlated with one another. In lumbar fluid neither compound appeared to be correlated with age. Analysis of serially collected lumbar samples from two subjects showed a weak concentration gradient for both compounds. Neither antipsychotic medication nor the acid transport inhibitor probenecid had any effect on lumbar concentrations of either compound. Attempts to use anion exchange high pressure liquid chromatography with UV detection for measurement of the low concentrations of N-acetylaspartate found in cerebrospinal fluid from living subjects were unsuccessful. PMID:10492520

Faull, K F; Rafie, R; Pascoe, N; Marsh, L; Pfefferbaum, A



Optimization of PIXE analysis for Cu and other trace elements in cerebrospinal fluid to improve the detection limits  

NASA Astrophysics Data System (ADS)

An external beam PIXE system was optimized for the determination of the extremely low trace element content of normal cerebrospinal fluid. In order to improve the detection limits of the elements of interest the ultrafiltrated cerebrospinal fluid samples were deposited onto ultrathin Formvar foils and measured in a helium atmosphere. Since the main emphasis was on copper, the absorber used in the measurements was optimized to give a favourable peak/background ratio for this element. The resulting detection limits for Fe, Cu, Zn and Br were (6.3+/-2.9), (4.1+/-1.4), (8.5+/-2.6) and (18.1+/-1.1) ppb, respectively. This allowed sufficiently precise determination of the low elemental concentrations in 50 ?l of human cerebrospinal fluid.

Kupila-Rantala, T.; Hyvönen-Dabek, M.; Dabek, J. T.



14-3-3 protein detection in the cerebrospinal fluid of patients with influenza-associated encephalopathy.  


Influenza-associated encephalopathy is characterized by high fever, convulsions, and loss of consciousness associated with influenza infection in children, but its pathophysiology remains to be clarified. We examined 14-3-3 proteins, which are acidic brain proteins, in cerebrospinal fluid by immunoblotting in four patients with influenza-associated encephalopathy, four patients with influenza without encephalopathy, and four patients with another encephalopathy. Interestingly, we detected 14-3-3 proteins in all four patients with influenza-associated encephalopathy (100%) but not in any of the other patients. 14-3-3 isoforms, including beta, gamma, epsilon, xi, and theta, were found in the cerebrospinal fluid of the patients with influenza-associated encephalopathy, suggesting extensive damage to the brain. We conclude that 14-3-3 proteins in cerebrospinal fluid are highly detectable in influenza-associated encephalopathy and thus can be used as a rapid diagnostic marker. PMID:16970844

Fujii, Katsunori; Tanabe, Yuzo; Uchikawa, Hideki; Kobayashi, Kazuhiko; Kubota, Hiroaki; Takanashi, Jun-ichi; Kohno, Yoichi



Effect of atrial natriuretic factor on permeability of the blood-cerebrospinal fluid barrier.  


The demonstration of 125I-labelled atrial natriuretic factor (ANF)-binding sites on choroid plexus suggests a physiological role of ANF on the blood-cerebrospinal fluid barrier. This ultrastructural study was undertaken to determine whether ANF (0.5 microgram) alters the permeability of rat blood-cerebrospinal fluid barrier under steady states. Horseradish peroxidase (HRP) was used as a marker of protein permeability and ionic lanthanum as a marker of ionic permeability. HRP was not observed in the walls of choroid plexus vessels of control rats at 3 or 6 min, while at 12 min HRP was present in vessel walls and occasionally in continuity in the adjacent intercellular space between choroidal epithelial cells. In ANF-treated rats, HRP was observed in vessel walls and in the intercellular space between the choroidal epithelial cells up to the apical tight junctions at 3 min, indicating an accelerated passage of tracer. Although HRP was never observed beyond the apical tight junctions in control or test animals, at 6 min test rats showed ionic lanthanum within these junctions in focal areas and in continuity in the adjacent ventricular cavity. These studies demonstrate that ANF causes accelerated passage of both HRP and ionic lanthanum from blood into choroid plexuses with passage of ionic lanthanum into the ventricular cavity through the apical tight junctions of choroidal epithelial cells. The latter is in keeping with the known function of ANF in regulating water and electrolyte fluxes. PMID:1836927

Nag, S



Cerebrospinal fluid beta-glucocerebrosidase activity is reduced in Dementia with Lewy Bodies.  


The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely beta-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus measured the activity of these enzymes - alpha-mannosidase (EC, beta-mannosidase (EC, beta-glucocerebrosidase (EC, beta-galactosidase (EC and beta-hexosaminidase (EC - in cerebrospinal fluid of patients suffering from DLB, Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and controls. Alpha-mannosidase activity showed a marked decrease across all the pathological groups as compared to controls. Conversely, beta-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies. PMID:19303930

Parnetti, L; Balducci, C; Pierguidi, L; De Carlo, C; Peducci, M; D'Amore, C; Padiglioni, C; Mastrocola, S; Persichetti, E; Paciotti, S; Bellomo, G; Tambasco, N; Rossi, A; Beccari, T; Calabresi, P



GWAS of cerebrospinal fluid tau levels identifies risk variants for Alzheimer's disease.  


Cerebrospinal fluid (CSF) tau, tau phosphorylated at threonine 181 (ptau), and A??? are established biomarkers for Alzheimer's disease (AD) and have been used as quantitative traits for genetic analyses. We performed the largest genome-wide association study for cerebrospinal fluid (CSF) tau/ptau levels published to date (n = 1,269), identifying three genome-wide significant loci for CSF tau and ptau: rs9877502 (p = 4.89 × 10?? for tau) located at 3q28 between GEMC1 and OSTN, rs514716 (p = 1.07 × 10?? and p = 3.22 × 10?? for tau and ptau, respectively), located at 9p24.2 within GLIS3 and rs6922617 (p = 3.58 × 10?? for CSF ptau) at 6p21.1 within the TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk. In independent data sets, rs9877502 showed a strong association with risk for AD, tangle pathology, and global cognitive decline (p = 2.67 × 10??, 0.039, 4.86 × 10??, respectively) illustrating how this endophenotype-based approach can be used to identify new AD risk loci. PMID:23562540

Cruchaga, Carlos; Kauwe, John S K; Harari, Oscar; Jin, Sheng Chih; Cai, Yefei; Karch, Celeste M; Benitez, Bruno A; Jeng, Amanda T; Skorupa, Tara; Carrell, David; Bertelsen, Sarah; Bailey, Matthew; McKean, David; Shulman, Joshua M; De Jager, Philip L; Chibnik, Lori; Bennett, David A; Arnold, Steve E; Harold, Denise; Sims, Rebecca; Gerrish, Amy; Williams, Julie; Van Deerlin, Vivianna M; Lee, Virginia M-Y; Shaw, Leslie M; Trojanowski, John Q; Haines, Jonathan L; Mayeux, Richard; Pericak-Vance, Margaret A; Farrer, Lindsay A; Schellenberg, Gerard D; Peskind, Elaine R; Galasko, Douglas; Fagan, Anne M; Holtzman, David M; Morris, John C; Goate, Alison M



Psychiatric patient stratification using biosignatures based on cerebrospinal fluid protein expression clusters.  


Psychiatric disorders are caused by perturbed molecular pathways that affect brain circuitries. The identification of specific biosignatures that are the result of altered pathway activities in major depression, bipolar disorder and schizophrenia can contribute to a better understanding of disease etiology and aid in the implementation of diagnostic assays. In the present study we identified disease-specific protein biosignatures in cerebrospinal fluid of depressed (n: 36), bipolar (n: 27) and schizophrenic (n: 35) patients using the Reverse Phase Protein Microarray technology. These biosignatures were able to stratify patient groups in an objective manner according to cerebrospinal fluid protein expression patterns. Correct classification rates were over 90%. At the same time several protein sets that play a role in neuronal growth, proliferation and differentiation (NEGR1, NPDC1), neurotransmission (SEZ6) and protection from oxidative damage (GPX3) were able to distinguish diseased from healthy individuals (n: 35) indicating a molecular signature overlap for the different psychiatric phenotypes. Our study is a first step toward implementing a psychiatric patient stratification system based on molecular biosignatures. Protein signatures may eventually be of use as specific and sensitive biomarkers in clinical trials not only for patient diagnostic and subgroup stratification but also to follow treatment response. PMID:23962679

Maccarrone, Giuseppina; Ditzen, Claudia; Yassouridis, Alexander; Rewerts, Christiane; Uhr, Manfred; Uhlen, Mathias; Holsboer, Florian; Turck, Christoph W



Embryonic cerebrospinal fluid collaborates with the isthmic organizer to regulate mesencephalic gene expression.  


Early in development, the behavior of neuroepithelial cells is controlled by several factors acting in a developmentally regulated manner. Recently it has been shown that diffusible factors contained within embryonic cerebrospinal fluid (CSF) promote neuroepithelial cell survival, proliferation, and neurogenesis in mesencephalic explants lacking any known organizing center. In this paper, we show that mesencephalic and mesencephalic+isthmic organizer explants cultured only with basal medium do not express the typically expressed mesencephalic or isthmic organizer genes analyzed (otx2 and fgf8, respectively) and that mesencephalic explants cultured with embryonic CSF-supplemented medium do effect such expression, although they exhibit an altered pattern of gene expression, including ectopic shh expression domains. Other trophic sources that are able to maintain normal neuroepithelial cell behavior, i.e., fibroblast growth factor-2, fail to activate this ectopic shh expression. Conversely, the expression pattern of the analyzed genes in mesencephalic+isthmic organizer explants cultured with embryonic cerebrospinal fluid-supplemented medium mimics the pattern for control embryos developed in ovo. We demonstrate that embryonic CSF collaborates with the isthmic organizer in regulation of the expression pattern of some characteristic neuroectodermal genes during early stages of central nervous system (CNS) development, and we suggest that this collaboration is not restricted to the maintenance of neuroepithelial cell survival. Data reported in this paper corroborate the hypothesis that factors contained within embryonic CSF contribute to the patterning of the CNS during early embryonic development. PMID:16180222

Parada, Carolina; Martín, Cristina; Alonso, María I; Moro, José A; Bueno, David; Gato, Angel



[Determination of tetramethylpyrazine in animal serum and cerebrospinal fluid by high performance liquid chromatography].  


A reversed-phase high performance liquid chromatographic (RP-HPLC) method for the determination of the tetramethylpyrazine(TMP) in Chuanxiong extract, the animal(mouse) serum and cerebrospinal fluid has been developed. The TMP was separated on an ODS column Zorbax SB-C18(4.6 mm i.d. x 250 mm, 5 microns) at room temperature and detected by using UV detector at 270 nm. The mobile phase was methanol-water (50:50, V/V) containing 0.2 mmol/L of NH4H2PO4 flowing at a rate of 0.8 mL/min and 20 microL samples were injected. The detection limit of TMP was 1 mg/L and the calibration curve is linear between 5 and 500 mg/L with a correlation coefficient (r) of 0.999. The recovery of TMP ranged 98%-103%. The extract of Chuanxiong and pretreated serum and cerebrospinal fluid sample are stable for a week at room temperature. PMID:12541454

Ding, M Y; Luo, S Z; Liu, H; Chen, P R; Liu, D L



Reassessing cerebrospinal fluid (CSF) hydrodynamics: a literature review presenting a novel hypothesis for CSF physiology.  


The traditional model of cerebrospinal fluid (CSF) hydrodynamics is being increasingly challenged in view of recent scientific evidences. The established model presumes that CSF is primarily produced in the choroid plexuses (CP), then flows from the ventricles to the subarachnoid spaces, and is mainly reabsorbed into arachnoid villi (AV). This model is seemingly based on faulty research and misinterpretations. This literature review presents numerous evidence for a new hypothesis of CSF physiology, namely, CSF is produced and reabsorbed throughout the entire CSF-Interstitial fluid (IF) functional unit. IF and CSF are mainly formed and reabsorbed across the walls of CNS blood capillaries. CP, AV and lymphatics become minor sites for CSF hydrodynamics. The lymphatics may play a more significant role in CSF absorption when CSF-IF pressure increases. The consequences of this complete reformulation of CSF hydrodynamics may influence applications in research, publications, including osteopathic manual treatments. PMID:23768280

Chikly, Bruno; Quaghebeur, Jörgen



Stabilization media increases recovery in paucicellular cerebrospinal fluid specimens submitted for flow cytometry testing.  


BACKGROUND: Flow cytometric immunophenotpying (FCI) of cerebrospinal fluid (CSF) and other paucicellular fluids has been demonstrated to have increased sensitivity in detection of lymphoma and leukemia when compared to cytomorphology [(1) de Graaf et al., Cytometry Part B 2011, 80B:271-281; (2) Szamosi et al., CLSI Document H56-A-Body Fluid Analysis for Cellular Composition; Approved Guideline, Wayne, PA: Clinical and Laboratory Standards Institute, 2006; (3) Kraan et al., Flow Cytometric Immunophenotyping of Cerebrospinal Fluid. Current Protocols in Cytometry, Hoboken, NJ: Wiley, 2008]. However, low cellularity has been an historical problem with these samples. Several studies indicate that immediate addition of a stabilization media (e.g., RPMI with fetal calf serum (FCS)) to CSF improves the cell yield for FCI [(1) de Graaf et al.]. Such stabilization medias can, however, significantly increase cost. METHODS: We compared FCI results in CSF stabilized with RPMI 1640 (without additional additives) to results obtained using non-stabilized CSF. Samples were processed according to published CLSI guidelines [(2) Szamosi et al.]. RESULTS: About 98/105 (93%) CSF specimens stabilized with RPMI had adequate numbers of viable cells (>100) for performing FCI. About 65/217 (30%) CSF specimens without stabilization had adequate numbers of viable cells for analysis (70% either quantity not sufficient (QNS) or specimen viability below analytical limits). CONCLUSIONS: Utilizing RMPI without FCS as a stabilization media results in increased cell yield and improved FCI results. We have found FCS is not required to achieve high quality results in FCI of paucicellular CSF specimens. © 2013 International Clinical Cytometry Society. PMID:23674507

Greig, B; Stetler-Stevenson, M; Lea, J



Brain-derived protein concentrations in the cerebrospinal fluid: contribution of trauma resulting from ventricular drain insertion.  


In recent years, the measurement of biomarkers following neurotrauma assisted in improving outcome prediction and guiding therapy. The use of neuroproteins as diagnostic parameters requires a detailed knowledge of their dynamics in biological fluids for an appropriate interpretation. S100B is the most widely studied neuromarker, and its concentration in serum and cerebrospinal fluid (CSF) reflects the extent of brain damage. Neuron-specific enolase (NSE) is considered reflecting neuronal damage, while Beta-Trace is a lepto-meningeal protein used to diagnose CSF leakage. In five patients treated with an external ventricular drain (EVD) because of aneurysmal subarachnoid hemorrhage (SAH, n=3) or postinfectious hydrocephalus (n=2), an EVD exchange was performed 8 to 12 days after initial insertion. S100B and NSE were measured with the Cobas e411(®) electrochemiluminescence assay (Roche Diagnostics, Mannheim, Germany) and Beta-Trace with the BN Pro Spec(®) nephelometer (Dade Behring/Siemens, Germany) 1?h before EVD exchange, upon the insertion of the new drain, and 1, 3, 6, 12, 18, 24 and 48?h after EVD exchange. Before EVD exchange, S100B CSF concentrations were within the normal range in all patients (1.48 ± 0.37??g/L), while NSE CSF concentrations were normal in four of five patients (6.51 ± 2.98??g/L). Following EVD exchange, S100B and NSE CSF levels peaked significantly at 3?h after insertion of the new drain (S100B 39.02 ± 9.17??g/L; NSE 54.80 ± 43.34??g/L). S100B serum levels were slightly increased 6 to 24?h after EVD exchange. Beta-Trace concentrations in the CSF were not altered by EVD insertion. Our data demonstrate that EVD insertion results in a distinct increase of S100B and NSE concentrations in the CSF. Thus, the tampering of brain-derived protein concentrations in the CSF by diagnostic or therapeutic procedures has to be considered in the interpretation of neuromarker levels. PMID:23390981

Brandner, Sebastian; Thaler, Christian; Buchfelder, Michael; Kleindienst, Andrea



Bacteroides fragilis meningitis successfully treated with metronidazole after a previous failure with thiamphenicol.  

PubMed Central

A case of pyogenic meningitis caused by Bacteroides fragilis in a 72-year-old woman is reported. Although the isolate was susceptible to thiamphenicol, the patient did not respond to this drug. Metronidazole, which showed high bactericidal activity, was administered and achieved sterilization of the cerebrospinal fluid and complete clinical response.

Soriano, F; Aguado, J M; Tornero, J; Fernandez-Guerrero, M L; Gomez-Garces, J L



Microsatellite typing and susceptibilities of serial Cryptococcus neoformans isolates from Cuban patients with recurrent cryptococcal meningitis  

Microsoft Academic Search

BACKGROUND: Cryptococcus neoformans is commonly associated with meningoencephalitis in immunocompromised patients and occasionally in apparently healthy individuals. Recurrence of infection after initial treatment is not uncommon. We studied C. neoformans isolates from 7 Cuban patients with recurrent cryptococcal meningitis. Antifungal susceptibility and genotyping with microsatellite molecular typing were carried out. METHODS: Isolates (n = 19) were recovered from cerebrospinal fluid,

María T Illnait-Zaragozí; Gerardo F Martínez-Machín; Carlos M Fernández-Andreu; Ferry Hagen; Teun Boekhout; Corné HW Klaassen; Jacques F Meis



Aseptic Meningitis and Encephalitis: the Role of PCR in the Diagnostic Laboratory  

Microsoft Academic Search

In this study we have devised a simple and robust PCR strategy to detect a wide range of viruses, bacteria, and parasites, all of which are capable of causing aseptic meningitis and encephalitis. The techniques developed have been used in a routine diagnostic virology laboratory to test prospectively 2,233 cerebrospinal fluid specimens. A virus was detected in 147 specimens of



Varicella zoster virus meningitis with hypoglycorrhachia in the absence of rash in an immunocompetent woman  

PubMed Central

We report varicella-zoster virus (VZV) meningitis in a healthy adult woman with no antecedent rash and with hypoglycorrhachia. Cerebrospinal fluid (CSF) examination revealed the presence of VZV DNA, anti-VZV immunoglobulin G (IgG) antibody, and intrathecal production of anti-VZV IgG antibody.

Habib, Ali A; Gilden, Don; Schmid, D Scott; Safdieh, Joseph E



Meningitis and Endocarditis Caused by Campylobacter fetus after Raw-Liver Ingestion.  


We report Campylobacter fetus meningitis associated with endocarditis in a 75-year-old diabetic man after he consumed raw liver. C. fetus was isolated from blood samples and cerebrospinal fluid. Cure was obtained with combined intravenous imipenem-gentamicin for 4 weeks; no relapse occurred after 6 months of follow-up. PMID:23824770

Suy, Florence; Le Dû, Damien; Roux, Anne-Laure; Hanachi, Mouna; Dinh, Aurélien; Crémieux, Anne-Claude



Association between excessive frontal cerebrospinal fluid and illness duration in males but not in females with schizophrenia  

Microsoft Academic Search

Objective. – Excessive cortical cerebrospinal fluid (CSF) has been acknowledged as a possible marker of a gray matter loss. This excess in schizophrenia is found predominantly in the prefrontal and temporal regions. We hypothesized that the poorer global outcome and treatment response in males with schizophrenia are related to a greater cortical volume loss as compared to females.Subjects and methods.

Vicente Molina; Javier Sanz; Fernando Sarramea; José M. Misiego; Carlos Benito; Tomás Palomo



ORIGINAL ARTICLE Cerebrospinal fluid and serum zinc, copper, magnesium and calcium levels in children with Idiopathic seizure  

Microsoft Academic Search

Objectives: The present study was conducted to observe the alteration and their relations in cerebrospinal fluid (CSF) and serum Zinc (Zn), Copper (Cu), Magnesium (Mg) and calcium (Ca) levels in patients with different types of idiopathic seizure and to determine the ratios of serum and CSF Ca\\/Mg and Cu\\/Zn. Methods: The children aged 1 to 14 years, having two or




Brain Metabolic Correlates of Cerebrospinal Fluid Beta-Amyloid 42 and Tau in Alzheimer’s Disease  

Microsoft Academic Search

Background: The cerebrospinal fluid (CSF) proteins ?-amyloid 42 (A?42) and Tau are believed to indirectly reflect some core pathological features of Alzheimer’s disease (AD). Their topographic origin and their association with synaptic dysfunction are still not well understood. Aim: The present study aimed to explore possible associations between cerebral glucose metabolism and CSF A?42 as well as Tau protein levels

Ruth Vukovich; Robert Perneczky; Alexander Drzezga; Hans Förstl; Alexander Kurz; Matthias Riemenschneider



Cerebrospinal fluid drainage and distal aortic perfusion: Reducing neurologic complications in repair of thoracoabdominal aortic aneurysm types I and II  

Microsoft Academic Search

Purpose: This study was conducted to evaluate the role of cerebrospinal fluid (CSF) drainage and distal aortic perfusion (DAP) in the prevention of postoperative neurologic complications for high-risk patients who had undergone type I and type II thoracoabdominal aortic aneurysm (TAAA) repair.Methods: CSF drainage and DAP were used as an adjunct in the treatment of 94 patients with TAAA (31

Hazim J. Safi; Kenneth R. Hess; Mark Randel; Dimitrios C. Iliopoulos; John C. Baldwin; Ravi K. Mootha; Salwa S. Shenaq; Roy Sheinbaum; Thomas Greene



Cerebrospinal fluid evidence of increased extra-mitochondrial glucose metabolism implicates mitochondrial dysfunction in multiple sclerosis disease progression  

Microsoft Academic Search

In contrast to relapse, the mechanisms of multiple sclerosis (MS) disease progression are less understood and appear not to be exclusively inflammatory in nature. In this pilot study we investigated the relationship between disturbed CNS energy metabolism and MS disease progression. We tested the hypothesis that cerebrospinal fluid (CSF) concentrations of sorbitol, fructose, and lactate, all metabolites of extra-mitochondrial glucose

William T. Regenold; Pornima Phatak; Michael J. Makley; Roger D. Stone; Mitchel A. Kling



Detection of Aspergillus DNA in Cerebrospinal Fluid from Patients with Cerebral Aspergillosis by a Nested PCR Assay  

Microsoft Academic Search

Invasive aspergillosis (IA), a complication with high mortality rates, especially in disseminated IA with cerebral involvement, is difficult to diagnose. Biopsy of cerebral lesions is often not feasible, and culture of Aspergillus spp. from cerebrospinal fluid (CSF) is frequently negative. New molecular methods have emerged for diagnosing IA. So far, there are only few reports of Aspergillus DNA detection in

M. Hummel; B. Spiess; K. Kentouche; S. Niggemann; C. Bohm; S. Reuter; M. Kiehl; H. Morz; R. Hehlmann; D. Buchheidt



Increases in cerebrospinal fluid caffeine concentration are associated with favorable outcome after severe traumatic brain injury in humans  

Microsoft Academic Search

Caffeine, the most widely consumed psychoactive drug and a weak adenosine receptor antagonist, can be neuroprotective or neurotoxic depending on the experimental model or neurologic disorder. However, its contribution to pathophysiology and outcome in traumatic brain injury (TBI) in humans is undefined. We assessed serial cerebrospinal fluid (CSF) concentrations of caffeine and its metabolites (theobromine, paraxanthine, and theophylline) by high-pressure

Kathleen T Sachse; Edwin K Jackson; Stephen R Wisniewski; Delbert G Gillespie; Ava M Puccio; Robert S B Clark; C Edward Dixon; Patrick M Kochanek



Cerebral venous and sinus thrombosis with cerebrospinal fluid circulation block after the first methotrexate administration by lumbar puncture  

Microsoft Academic Search

We report a patient treated for small lymphocytic lymphoma\\/leukemia with cerebral venous and sinus thrombosis (CVST) after lumbar puncture with intrathecal administration of methotrexate (MTX). He also developed a cerebrospinal fluid flow block. This is the first report of an association between lumbar puncture and intrathecally administered MTX and the development of CVST. Intrathecal treatment in this patient was discontinued

H. P. Bienfait; J. Gijtenbeek; M. van den Bent; H. de Bruin; P. Voogt; M. Pillay



Rapid determination of piracetam in human plasma and cerebrospinal fluid by micellar electrokinetic chromatography with sample direct injection  

Microsoft Academic Search

A simple micellar electrokinetic chromatography (MEKC) method with UV detection at 200nm for analysis of piracetam in plasma and in cerebrospinal fluid (CSF) by direct injection without any sample pretreatment is described. The separation of piracetam from biological matrix was performed at 25°C using a background electrolyte consisting of Tris buffer with sodium dodecyl sulfate (SDS) as the electrolyte solution.

Hsin-Hua Yeh; Yuan-Han Yang; Ju-Yun Ko; Su-Hwei Chen



Altered kallikrein 7 and 10 concentrations in cerebrospinal fluid of patients with Alzheimer's disease and frontotemporal dementia  

Microsoft Academic Search

Background: The role of various proteases in the pathogenesis of Alzheimer's disease is well documented. Recently, many members of the human tissue kallikrein family, a group of 15 secreted serine proteases, were found to be highly expressed in the central nervous system (CNS). Some of these enzymes can be measured in cerebrospinal fluid (CSF) by using ELISA-type methodologies.Methods: We quantified

Eleftherios P Diamandis; Andreas Scorilas; Tadaaki Kishi; Kaj Blennow; Liu-Ying Luo; Antoninus Soosaipillai; Alfred W Rademaker; Magnus Sjogren



Fear and power-dominance motivation: proposed contributions of peptide hormones present in cerebrospinal fluid and plasma  

Microsoft Academic Search

We propose that fear and power-dominance drive motivation are generated by the presence of elevated plasma and cerebrospinal fluid (CSF) levels of certain peptide hormones. For the fear drive, the controlling hormone is corticotropin releasing factor, and we argue that elevated CSF and plasma levels of this peptide which occur as a result of fear-evoking and other stressful experiences in

Terence V. Sewards; Mark A. Sewards



Identification of nociceptin in human cerebrospinal fluid: comparison of levels in pain and non-pain states  

Microsoft Academic Search

We have measured plasma and cerebrospinal fluid (CSF) concentrations of nociceptin, the endogenous agonist of the orphan opioid receptor-like receptor (ORL- 1). We studied two groups of ten patients presenting for elective Caesarean section (Group E) or in established labour and requiring combined spinal epidural anaesthesia for pain relief (Group L). Nociceptin was identified in all CSF samples with mean±SD

H Brooks; C. D Elton; D Smart; D. J Rowbotham; A. T McKnight; D. G Lambert



Asymmetrical Dimethylarginine Is Increased in Plasma and Decreased in Cerebrospinal Fluid of Patients with Alzheimer’s Disease  

Microsoft Academic Search

Background: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase and may alter NO production during pathological conditions. Concerning Alzheimer’s disease (AD), there are reports on altered cerebral NO metabolism, but only few studies on ADMA concentrations in plasma and cerebrospinal fluid (CSF). Methods: We assessed plasma ADMA in 80 AD patients and 80 age- and gender-matched

Sönke Arlt; Friedrich Schulze; Martin Eichenlaub; Renke Maas; Jan T. Lehmbeck; Edzard Schwedhelm; Holger Jahn; Rainer H. Böger



Decrease of E and EA but Not EAC Rosette Formation after Incubation of Blood Lymphocytes in Cerebrospinal Fluid  

Microsoft Academic Search

Peripheral blood lymphocytes (PBL) were incubated in autologous cerebrospinal fluid (CSF) or Hanks’ balanced salt solution (HBSS) for between 5 and 60 min at 37 °C. Incubation in CSF caused an increase in cell death as measured by trypan blue inclusion. Incubation in CSF also resulted in a decreased percentage of E and EA rosette-forming cells (RFC) – but not

A. Næss



Antibodies in Cerebrospinal Fluid of Some Alzheimer Disease Patients Recognize Cholinergic Neurons in the Rat Central Nervous System  

Microsoft Academic Search

The etiology of Alzheimer disease is unclear. However, immunological aberrations have been suggested to be critical factors in the pathogenesis of this neurodegenerative disease. This study was carried out to investigate if cerebrospinal fluid (CSF) from Alzheimer disease patients contains antibodies that recognize specific neuronal populations in the rat central nervous system. The results indicate that in a subgroup of

Amanda McRae-Degueurce; Serney Booj; Kenneth Haglid; Lars Rosengren; Jan Erik Karlsson; Ingvar Karlsson; Anders Wallin; Lars Svennerholm; Carl-Gerhard Gottfries; Annica Dahlstrom



Cerebrospinal Fluid Leptin in Anorexia Nervosa: Correlation with Nutritional Status and Potential Role in Resistance to Weight Gain  

Microsoft Academic Search

Studies in rodents have shown that leptin acts in the central ner- vous system to modulate food intake and energy metabolism. To evaluate the possible role of leptin in the weight loss of anorexia nervosa, this study compared cerebrospinal fluid (CSF) and plasma leptin concentrations in anorexic patients and controls. Subjects in- cluded 11 female patients with anorexia nervosa studied




Excitability of neurons in the ventromedial nucleus in rat hypothalamic slices: modulation by amino acids at cerebrospinal fluid levels  

Microsoft Academic Search

Free amino acid composition of cerebrospinal fluid (CSF) in the rat was measured to examine if electrical activity of neurons in the ventromedial nucleus of the hypothalamus (VMH) is modulated by amino acids at CSF levels. In CSF collected through a cannula in the cerebromedullary cistern of freely moving rats, the total concentration of amino acids was 979 ?M, while

Fusae Nishimura; Masugi Nishihara; Masato Mori; Kunio Torii; Michio Takahashi



Detection of Measles Virus Genomic RNA in Cerebrospinal Fluid of Children with Regressive Autism: a Report of Three Cases  

Microsoft Academic Search

In light of encephalopathy presenting as autistic regression (autistic encephalopathy, AE) closely following measles-mumps- rubella (MMR) vaccination, three children underwent cerebrospinal fluid (CSF) assessments including studies for measles virus (MV). All three children had concomitant onset of gastrointestinal (GI) symptoms and had already had MV genomic RNA detected in biopsies of ileal lymphoid nodular hyperplasia (LNH). Presence of MV Fusion

J. J. Bradstreet; J. El Dahr; A. Anthony; J. J. Kartzinel; A. J. Wakefield



Disturbances of the clotting and anticlotting system of the blood and cerebrospinal fluid in experimental brain trauma  

Microsoft Academic Search

In the course of an experimental study of the effect of brain trauma on the structure of the vascular system of the choroid plexuses,the writer noted that, besides a disturbance of the coagulability of the blood, components of the clotting and anticlotting systems appear in the cerebrospinal fluid (CSF). After brain trauma, thechemieal composition of the CSF is known to

Vo P. Yurchenko



Transforming growth factor-?1 levels are elevated in the striatum and in ventricular cerebrospinal fluid in Parkinson's disease  

Microsoft Academic Search

Transforming growth factor (TGF)-?1 content was measured for the first time in the brain (caudate nucleus, putamen, and cerebral cortex) and in ventricular cerebrospinal fluid (VCSF) from control and parkinsonian patients by a sandwich enzyme immunoassay. The concentrations of TGF-?1 were significantly higher in the dopaminergic striatal regions in parkinsonian patients than those in controls, but were not significantly different

Makio Mogi; Minoru Harada; Tomoyoshi Kondo; Hirotaro Narabayashi; Peter Riederer; Toshiharu Nagatsu



Cerebrospinal fluid of Alzheimer's disease and dementia with Lewy bodies patients enhances ?-synuclein fibril formation in vitro  

Microsoft Academic Search

Deposition of ?-synuclein (?S) aggregates inside brain cells is a pathological hallmark of several neurodegenerative diseases, including Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Recently, extracellular ?S was detected in cerebrospinal fluid (CSF) and plasma of humans. We investigated whether CSF influences ?S aggregation in vitro using fluorescence spectroscopy with thioflavin S and electron microscopy. We found that

Kenjiro Ono; Moeko Noguchi-Shinohara; Mitsuhiro Yoshita; Hironobu Naiki; Masahito Yamada



Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species  

Microsoft Academic Search

BACKGROUND: The parenchyma of the brain does not contain lymphatics. Consequently, it has been assumed that arachnoid projections into the cranial venous system are responsible for cerebrospinal fluid (CSF) absorption. However, recent quantitative and qualitative evidence in sheep suggest that nasal lymphatics have the major role in CSF transport. Nonetheless, the applicability of this concept to other species, especially to

Miles Johnston; Andrei Zakharov; Christina Papaiconomou; Giselle Salmasi; Dianna Armstrong



A flexible metal ventricular catheter for treatment of complicated and protracted infections of the cerebrospinal fluid spaces: Preliminary experiences  

Microsoft Academic Search

Summary In the management of shunt infection, the use of ventricular catheters made of silicone rubber for the temporary external drainage of cerebrospinal fluid (CSF) is general practice. However, the eradication of the primary source of infection may be hindered by the affinity of bacteria to silicone-based material. Compared to silicone catheters, a metal drainage device for temporary ventriculostomy appears

U. Vieweg; B. Kaden; D. Van Roost



Improved resolution of human cerebrospinal fluid proteins on two-dimensional gels.  


Proteomics combines two-dimensional gel electrophoresis and peptide mass fingerprinting and can potentially identify a protein(s) unique to disease. Such proteins can be used either for diagnosis or may be relevant to the pathogenesis of disease. Because patients with multiple sclerosis (MS) have increased amounts of immunoglobulin (Ig) G in their cerebrospinal fluid (CSF) that is directed against an as yet unidentified protein, we are applying proteomics to MS CSF, studies that require optimal separation of proteins in human CSF. We found that recovery of proteins from CSF of MS patients was improved using ultrafiltration, rather than dialysis, for desalting. Resolution of these proteins was enhanced by acetone precipitation of desalted CSF before electrophoresis and by fractionation of CSF using Cibacron Blue sepharose affinity chromatography. Improved protein recovery and resolution will facilitate excision from gels for analysis by peptide mass fingerprinting. PMID:14582772

Hammack, B N; Owens, G P; Burgoon, M P; Gilden, D H



Cerebrospinal fluid anandamide levels, cannabis use and psychotic-like symptoms.  


Anandamide is a ligand of the endocannabinoid system. Animals show a depletion following repeated ?(9)-tetrahydrocannabinol (THC) administration but the effect of cannabis use on central nervous system levels of endocannabinoids has not been previously examined in humans. Cerebrospinal fluid (CSF) levels of the endocannabinoids anandamide, 2-arachidonoylglycerol (2-AG) and related lipids were tested in 33 volunteers (20 cannabis users). Lower levels of CSF anandamide and higher levels of 2-AG in serum were observed in frequent compared with infrequent cannabis users. Levels of CSF anandamide were negatively correlated with persisting psychotic symptoms when drug-free. Higher levels of anandamide are associated with a lower risk of psychotic symptoms following cannabis use. PMID:23580381

Morgan, Celia J A; Page, Emma; Schaefer, Carola; Chatten, Katharine; Manocha, Amod; Gulati, Sumit; Curran, H Valerie; Brandner, Brigitta; Leweke, F Markus



Effects of spatial variation of skull and cerebrospinal fluid layers on optical mapping of brain activities  

NASA Astrophysics Data System (ADS)

In order to investigate the effects of anatomical variation in human heads on the optical mapping of brain activity, we perform simulations of optical mapping by solving the photon diffusion equation for layered-models simulating human heads using the finite element method (FEM). Particularly, the effects of the spatial variations in the thicknesses of the skull and cerebrospinal fluid (CSF) layers on mapping images are investigated. Mapping images of single active regions in the gray matter layer are affected by the spatial variations in the skull and CSF layer thicknesses, although the effects are smaller than those of the positions of the active region relative to the data points. The increase in the skull thickness decreases the sensitivity of the images to active regions, while the increase in the CSF layer thickness increases the sensitivity in general. The images of multiple active regions are also influenced by their positions relative to the data points and by their depths from the skin surface.

Wang, Shuping; Shibahara, Nanae; Kuramashi, Daishi; Okawa, Shinpei; Kakuta, Naoto; Okada, Eiji; Maki, Atsushi; Yamada, Yukio



Elevated glial fibrillary acidic protein levels in the cerebrospinal fluid of patients with narcolepsy.  


Glial fibrillary acidic protein (GFAP) is an established indicator of astrogliosis. Therefore, variable cerebrospinal fluid (CSF) concentrations of this protein might reflect disease-specific pathologic profiles. In patients with narcolepsy, a loss of hypocretin-1 (hcrt-1) neurons in the brain and low concentrations of hcrt-1 in CSF have been reported. We performed a commercially available enzyme-linked immunosorbent assay to investigate if GFAP also is altered in the CSF of these patients. Here we detected significantly higher CSF levels of GFAP in patients with low hcrt-1 levels, of which the majority had a diagnosis of narcolepsy and cataplexy (NC); however, this finding was not observed in patients with hcrt-1 levels that were within reference range. In conclusion, GFAP may be useful as an additional disease biomarker in patients with narcolepsy, and this hypothesis should be investigated in larger studies. PMID:23746601

Feneberg, Emily; Steinacker, Petra; Lehnert, Stefan; Böhm, Bernhard; Mayer, Geert; Otto, Markus



Plasma Cell Cerebrospinal Fluid Pleocytosis Does Not Predict West Nile Virus Infection  

PubMed Central

Purpose. Diagnosis of WNV (WNV) relies upon serologic testing which may take several days after the onset of clinical symptoms to turn positive. Anecdotal reports suggest the presence of plasma cells or plasmacytoid lymphocytes in the cerebrospinal fluid (CSF) may be an early indicator of WNV infection. Methods. The CSFs of 89 patients (12 with WNV, 12 with other viral illness {OVI}, and 65 with nonviral illness{NVI}) were compared for the presence of either plasma cells or plasmacytoid lymphocytes. Results. Plasma cells were rarely seen in any of the patients. Plasmacytoid lymphocytes were more commonly seen in WNV (58%) and OVI (50%) than NVI (11%). The differences were significant for WNV versus NVI, but not WNV versus OVI (P < 0.001 and P = 0.58, resp.). Conclusions. A CSF pleocytosis with plasma cells or plasmacytoid lymphocytes was neither sensitive nor specific for the diagnosis of WNV infection.

Jordan, Michael; Nagpal, Avish; Newman, William; Thompson, Paul A.; Carson, Paul J.



Do genes and environment meet to regulate cerebrospinal fluid dynamics? Relevance for schizophrenia  

PubMed Central

Schizophrenia is a neurodevelopment disorder in which the interplay of genes and environment contributes to disease onset and establishment. The most consistent pathological feature in schizophrenic patients is an enlargement of the brain ventricles. Yet, so far, no study has related this finding with dysfunction of the choroid plexus (CP), the epithelial cell monolayer located within the brain ventricles that is responsible for the production of most of the cerebrospinal fluid (CSF). Enlarged brain ventricles are already present at the time of disease onset (young adulthood) and, of notice, isolated mild ventriculomegaly detected in utero is associated with subsequent mild neurodevelopmental abnormalities similar to those observed in children at high risk of developing schizophrenia. Here we propose that altered CP/CSF dynamics during neurodevelopment may be considered a risk, causative and/or participating factor for development of schizophrenia.

Palha, Joana A.; Santos, Nadine C.; Marques, Fernanda; Sousa, Joao; Bessa, Joao; Miguelote, Rui; Sousa, Nuno; Belmonte-de-Abreu, Paulo



Jacalin-unbound fraction of Taenia saginata in immunodiagnosis of neurocysticercosis in human cerebrospinal fluid.  


The aim of this study was to evaluate jacalin-bound fraction (JBF) and jacalin-unbound fraction (JUF) of the total saline extract from Taenia saginata metacestodes for human neurocysticercosis (NC) immunodiagnosis in cerebrospinal fluid. Total extract, JBF, and JUF were separated by affinity chromatography using Sepharose(®)-jacalin and were tested in enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB) to detect immunoglobulin G. In ELISA test, JUF showed the higher diagnostic efficiency and specificity indexes, 92% and 100%, respectively. In WB, 5 immunodominant proteins (39-42, 47-52, 64-68, 70, and 75 kDa) were detected when using JUF. In conclusion, the results achieved demonstrate that JUF, obtained from T. saginata metacestodes, are an important source of specific peptides and are efficient in the diagnosis of NC. PMID:20846809

da Silva Nunes, Daniela; da Silva Ribeiro, Vanessa; Manhani, Marianna Nascimento; Costa-Cruz, Julia Maria



Metal concentrations in cerebrospinal fluid and blood plasma from patients with amyotrophic lateral sclerosis.  


Amyotrophic lateral sclerosis (ALS) is a progressive and fatal degenerative disorder of motor neurons. The cause of this degeneration is unknown, and different causal hypotheses include genetic, viral, traumatic and environmental mechanisms. In this study, we have analyzed metal concentrations in cerebrospinal fluid (CSF) and blood plasma in a well-defined cohort (n = 17) of ALS patients diagnosed with quantitative electromyography. Metal analyses were performed with high-resolution inductively coupled plasma mass spectrometry. Statistically significant higher concentrations of manganese, aluminium, cadmium, cobalt, copper, zinc, lead, vanadium and uranium were found in ALS CSF compared to control CSF. We also report higher concentrations of these metals in ALS CSF than in ALS blood plasma, which indicate mechanisms of accumulation, e.g. inward directed transport. A pattern of multiple toxic metals is seen in ALS CSF. The results support the hypothesis that metals with neurotoxic effects are involved in the pathogenesis of ALS. PMID:23225075

Roos, Per M; Vesterberg, Olof; Syversen, Tore; Flaten, Trond Peder; Nordberg, Monica



Interpretation of positive molecular tests of common viruses in the cerebrospinal fluid.  


Many central nervous system infections are historically difficult to diagnose. Polymerase chain reaction (PCR) has revolutionized the diagnosis of these infections because of their high sensitivity despite the lack of data on clinical usefulness. We conducted a retrospective study that included patients with positive cerebrospinal fluid (CSF) PCR for herpes simplex virus, varicella-zoster virus, JC virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV) between January 2009 and December 2011. The positive results were grouped into definite, likely, and possible true positives and likely false-positive categories based on pre-specified definitions specific to each virus. Of 1663 CSF viral PCR tests, 88 were positive (5%). The combined positive predictive value (PPV) was 58%. The PPVs were least for CMV and EBV at 29 and 37%, respectively. A positive CSF viral PCR result has to be interpreted with caution due to several false-positive results. PMID:24035384

Bhaskaran, Archana; Racsa, Lori; Gander, Rita; Southern, Paul; Cavuoti, Dominick; Alatoom, Adnan



A Window into the Heterogeneity of Human Cerebrospinal Fluid A? Peptides  

PubMed Central

The initiating event in Alzheimer's disease (AD) is an imbalance in the production and clearance of amyloid beta (A?) peptides leading to the formation of neurotoxic brain A? assemblies. Cerebrospinal Fluid (CSF), which is a continuum of the brain, is an obvious source of markers reflecting central neuropathologic features of brain diseases. In this review, we provide an overview and update on our current understanding of the pathobiology of human CSF A? peptides. Specifically, we focused our attention on the heterogeneity of the CSF A? world discussing (1) basic research studies and what has been translated to clinical practice, (2) monomers and other soluble circulating A? assemblies, and (3) communication modes for A? peptides and their microenvironment targets. Finally, we suggest that A? peptides as well as other key signals in the central nervous system (CNS), mainly involved in learning and hence plasticity, may have a double-edged sword action on neuron survival and function.

Ghidoni, Roberta; Paterlini, Anna; Albertini, Valentina; Stoppani, Elena; Binetti, Giuliano; Fuxe, Kjell; Benussi, Luisa; Agnati, Luigi F.



Scanning electron microscopic observations of the arachnoid granulations in monkeys with cerebrospinal fluid hypotension.  


The changes in arachnoid granulations following the depletion of cerebrospinal fluid (CSF) were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In the normal tissue, the arachnoid granulations located at the inner walls of the superior sagittal sinus and the straight sinus had bulging protrusions of various sizes, as viewed with the SEM. With TEM, the outermost cells covering the surface of the arachnoid granulations had "giant vacuoles" in the cytoplasm. With CSF hypotension, the arachnoid granulations were smaller in size and the outermost layer of cells were thinner. The vacuoles in the outer layer were not developed. In the apical region of the individual arachnoid granulations with CSF hypotension, the arachnoid cells were densely clustered under the endothelial cells. With recovery to normal CSF pressure, the arachnoid cells appeared to protrude between the endothelial cells covering the apical portion of the arachnoid granulation. PMID:8007628

Takahashi, Y; Shigemori, M; Inokuchi, T; Miyajima, S; Maehara, T; Wakimoto, M; Matsuo, H



Effects of aluminum chloride on the rate of secretion of the cerebrospinal fluid  

SciTech Connect

The claim that AlCl/sub 3/ could produce 100% inhibition of cerebrospinal fluid secretion was investigated using ventriculocisternal perfusion in the rabbit, and it was shown that a large part of this inhibition was an artefact due to a pH sensitivity of Blue Dextran, used as an indiffusible marker, caused by AlCl/sub 3/. Thus the true inhibition found, using (/sup 3/H)labeled markers, was about 33% and usually only partly reversible. Penetration of /sup 22/Na from blood into the perfused ventricles was partially inhibited by AlCl/sub 3/. The effects of some other acid buffer systems, namely acetate and phosphate, on rate of secretion were measured; the results were highly variable. When mean arterial pressure was measured, it was found to be unaffected by AlCl/sub 3/ but elevated with acetate and phosphate buffer mixtures.

Zlokovic, B.V.; Davson, H.; Preston, J.E.; Segal, M.B.



Cerebrospinal fluid immunoreactive substance P and somatostatin in neurological patients with peripheral and spinal cord disease.  


We have measured substance P-like (SPLI) and somatostatin-like (SLI) immunoreactivities in cerebrospinal fluid of 49 patients with peripheral (polyneuropathy, lumboischialgia) and spinal cord disease and in 16 control patients. The patient groups showed significantly higher CSF SPLI levels than controls while the mean SLI levels were unchanged. Fractionated sampling of CSF (total volume 30 ml) in 20 patients with various neurological diseases showed no significant differences between early and late fractions for SLI. In contrast, lumbar-cisternal concentration gradients were negative for SPLI, total protein and IgG, and positive for the dopamine metabolite homovanillic acid and the serotonin metabolite 5-hydroxyindolacetic acid. This suggests that SPLI may be released into the lumbar CSF from lower levels of the neuraxis, presumably the spinal cord and spinal ganglia, whereas SLI stems from diffuse CSF secretion without spinal preponderance. PMID:2468107

Cramer, H; Rösler, N; Rissler, K; Gagnieu, M C; Renaud, B



Detection of immunoglobulin M in cerebrospinal fluid from syphilis patients by enzyme-linked immunosorbent assay.  

PubMed Central

Cerebrospinal fluid (CSF) samples were evaluated in an immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) for syphilis with sonic extracts of Treponema pallidum coated on polystyrene plates. The ELISA procedure was reproducible, and T. pallidum antigens were stable., A total of 15 CSF samples from patients with neurosyphilis, 18 CSF samples from patients with syphilis, 12 CSF samples from patients treated for syphilis, and 494 CSF samples from patients with neurologic or other systemic diseases were tested. The IgM ELISA gave reactive results in all of six symptomatic and congenital neurosyphilitic patients and none of nine asymptomatic neurosyphilitic patients. Of 524 CSF samples from nonneurosyphilitic individuals, 513 were nonreactive, resulting in 98% test specificity. The IgM ELISA in CSF should prove to be useful for confirmation of symptomatic neurosyphilis.

Lee, J B; Farshy, C E; Hunter, E F; Hambie, E A; Wobig, G H; Larsen, S A



Normal pressure hydrocephalus. Influences on cerebral hemodynamic and cerebrospinal fluid pressure--chemical autoregulation  

SciTech Connect

Blood flow in the cerebral gray matter was measured in normal pressure hydrocephalus and Alzheimer disease by 133Xe inhalation. Flow values in the frontal and temporal gray matter increased after lowering cerebrospinal fluid (CSF) pressure by lumbar puncture in normal pressure hydrocephalus (p less than 0.05) and also after shunting. One case with cerebral complications did not improve clinically. In Alzheimer disease the reverse (decreases in flow in the gray matter) occurred after removal of CSF. Normal pressure hydrocephalus was associated with impaired cerebral vasomotor responsiveness during 100% oxygen and 5% carbon dioxide inhalation. This complication was restored toward normal after CSF removal and/or shunting. Cerebral blood flow measurements appear to be useful for confirming the diagnosis of normal pressure hydrocephalus and predicting the clinical benefit from shunting.

Meyer, J.S.; Tachibana, H.; Hardenberg, J.P.; Dowell, R.E. Jr.; Kitagawa, Y.; Mortel, K.F.



Plasma oxytocin and vasopressin do not predict neuropeptide concentrations in human cerebrospinal fluid.  


The involvement of the neuropeptides oxytocin (OXT) and vasopressin (AVP) in human socio-emotional behaviours is attracting increasing attention. There is ample evidence for elevated plasma levels upon a wide variety of social and emotional stimuli and scenarios, ranging from romantic love via marital distress up to psychopathology, with cause versus consequence being largely unclear. The present study examined whether plasma levels of both OXT and AVP are reflective of central neuropeptide levels, as assumed to impact upon socio-emotional behaviours. Concomitant plasma and cerebrospinal fluid (CSF) samples were taken from 41 non-neurological and nonpsychiatric patients under basal conditions. Although OXT and AVP levels in the CSF exceeded those in plasma, there was no correlation between both compartments, clearly suggesting that plasma OXT and AVP do not predict central neuropeptide concentrations. Thus, the validity of plasma OXT and AVP as potential biomarkers of human behaviour needs further clarification. PMID:23574490

Kagerbauer, S M; Martin, J; Schuster, T; Blobner, M; Kochs, E F; Landgraf, R



Cerebrospinal fluid viral breakthrough in two HIV-infected subjects on darunavir/ritonavir monotherapy  

PubMed Central

Darunavir/ritonavir monotherapy maintains HIV suppression in most patients who have achieved an undetectable viral load on combination antiretroviral treatment, and is increasingly used in the clinic. However, concerns have been raised about the effectiveness of ritonavir-boosted protease inhibitor (PI/r) monotherapy in the prevention of HIV replication in the central nervous system (CNS). Here we report the cases of 2 patients on darunavir/r maintenance monotherapy with cerebrospinal fluid viral breakthrough together with increased immunoactivation and biomarker signs of neuronal injury. These 2 cases raise concerns about the effectiveness of darunavir/ritonavir monotherapy in HIV CNS infection. Thus, we recommend caution with protease inhibitor monotherapy until CNS results have been obtained from clinical studies.



Antibodies to varicella zoster virus in the cerebrospinal fluid of neonates with seizures  

PubMed Central

Four neonates with convulsions had IgG antibodies in their cerebrospinal fluid (CSF) to varicella zoster virus (VZV). These antibodies were found in the sera of two of these patients after the age of 6 months. Antibodies to 16 different microbes were studied from the serum and CSF of 201 neonates with neurological problems. The presence of DNA specific to HSV-1, HSV-2, and VZV in the CSF was also investigated using the polymerase chain reaction (PCR). Antibodies to VZV were detected in the CSF of four neonates. Antibody indices suggested production of VZV specific antibodies in the central nervous system. These findings suggest that intrathecal production of antibodies to VZV can appear in neonates with neurological problems, which suggests that intrauterine VZV infection can be acquired without cutaneous symptoms in the mother.??

Mustonen, K.; Mustakangas, P.; Smeds, M.; Mannonen, L.; Uotila, L.; Vaheri, A.; Koskiniemi, M.



Biomarkers for severity of spinal cord injury in the cerebrospinal fluid of rats.  


One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage. PMID:21559420

Lubieniecka, Joanna M; Streijger, Femke; Lee, Jae H T; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K; Coorssen, Jens R; Foster, Leonard J; Grigliatti, Thomas A; Tetzlaff, Wolfram



Biomarkers for Severity of Spinal Cord Injury in the Cerebrospinal Fluid of Rats  

PubMed Central

One of the major challenges in management of spinal cord injury (SCI) is that the assessment of injury severity is often imprecise. Identification of reliable, easily quantifiable biomarkers that delineate the severity of the initial injury and that have prognostic value for the degree of functional recovery would significantly aid the clinician in the choice of potential treatments. To find such biomarkers we performed quantitative liquid chromatography-mass spectrometry (LC-MS/MS) analyses of cerebrospinal fluid (CSF) collected from rats 24 h after either a moderate or severe SCI. We identified a panel of 42 putative biomarkers of SCI, 10 of which represent potential biomarkers of SCI severity. Three of the candidate biomarkers, Ywhaz, Itih4, and Gpx3 were also validated by Western blot in a biological replicate of the injury. The putative biomarkers identified in this study may potentially be a valuable tool in the assessment of the extent of spinal cord damage.

Lubieniecka, Joanna M.; Streijger, Femke; Lee, Jae H. T.; Stoynov, Nikolay; Liu, Jie; Mottus, Randy; Pfeifer, Tom; Kwon, Brian K.; Coorssen, Jens R.; Foster, Leonard J.; Grigliatti, Thomas A.; Tetzlaff, Wolfram



Metabolic clearance of insulin from the cerebrospinal fluid in the anesthetized rat  

SciTech Connect

Infusion of 125I-(Tyr A14)-insulin at tracer doses into the cerebrospinal fluid (CSF) resulted in a slow rate of increase in the CSF-labeled insulin during the first 2 hours with a plateau thereafter. Labeled insulin was cleared from the CSF at a higher rate than 3H-inulin, a marker of CSF bulk flow. The labeled insulin was mainly distributed in all the ventricular and periventricular brain regions. Small amounts of degraded insulin appeared in the CSF. Coinfusion with an excess of unlabeled insulin impaired the clearance and degradation of labeled insulin. It also inhibited the labeling in medial hypothalamus, olfactory bulbs and brain stem. In contrast, coinfusion of ribonuclease B (used to test the specificity of uptake) was without any effect. It was concluded that there is an active insulin intake from CSF into brain specific compartments that is presumably essential for the effects of insulin on brain function.

Manin, M.; Broer, Y.; Balage, M.; Rostene, W.; Grizard, J. (Laboratoire d'etude du Metabolisme Azote, Ceyrat (France))



Identification of a New Cyclovirus in Cerebrospinal Fluid of Patients with Acute Central Nervous System Infections  

PubMed Central

ABSTRACT Acute central nervous system (CNS) infections cause substantial morbidity and mortality, but the etiology remains unknown in a large proportion of cases. We identified and characterized the full genome of a novel cyclovirus (tentatively named cyclovirus-Vietnam [CyCV-VN]) in cerebrospinal fluid (CSF) specimens of two Vietnamese patients with CNS infections of unknown etiology. CyCV-VN was subsequently detected in 4% of 642 CSF specimens from Vietnamese patients with suspected CNS infections and none of 122 CSFs from patients with noninfectious neurological disorders. Detection rates were similar in patients with CNS infections of unknown etiology and those in whom other pathogens were detected. A similar detection rate in feces from healthy children suggested food-borne or orofecal transmission routes, while high detection rates in feces from pigs and poultry (average, 58%) suggested the existence of animal reservoirs for such transmission. Further research is needed to address the epidemiology and pathogenicity of this novel, potentially zoonotic virus.

Tan, Le Van; van Doorn, H. Rogier; Nghia, Ho Dang Trung; Chau, Tran Thi Hong; Tu, Le Thi Phuong; de Vries, Michel; Canuti, Marta; Deijs, Martin; Jebbink, Maarten F.; Baker, Stephen; Bryant, Juliet E.; Tham, Nguyen Thi; BKrong, Nguyen Thi Thuy Chinh; Boni, Maciej F.; Loi, Tran Quoc; Phuong, Le Thi; Verhoeven, Joost T. P.; Crusat, Martin; Jeeninga, Rienk E.; Schultsz, Constance; Chau, Nguyen Van Vinh; Hien, Tran Tinh; van der Hoek, Lia; Farrar, Jeremy; de Jong, Menno D.



Meningitis caused by Rhodotorula rubra in an human immunodeficiency virus infected patient.  


Rhodotorula spp. are common saprophytes but may be responsible for systemic infections in immunocompromised patients. Meningitis caused by Rhodotorula spp. in human immunodeficiency virus (HIV) infected patients has been reported only rarely. We present a case of meningitis caused by Rhodotorula rubra in HIV infected patient. The presumptive diagnosis of cryptococcal meningitis was made on the basis of India ink preparation, Gram staining and latex agglutination test (LAT) for cryptococcal antigen. The final diagnosis was confirmed by isolation of Rhodotorula rubra from cerebrospinal fluid on culture. LAT was considered false positive. Amphotericin B and 5-fluorocytosine were administered but the patient succumbed to his illness. PMID:17582194

Thakur, K; Singh, G; Agarwal, S; Rani, L



A 59-year-old woman with tuberculous meningitis masked by hepatic encephalopathy.  


Tuberculous meningitis is a difficult diagnosis to make. The presenting symptoms, signs, and laboratory values are often nonspecific and can be attributed to other underlying conditions. Imaging and cerebrospinal fluid analysis can be more helpful. Extra pulmonary tuberculosis is not uncommon, and tuberculous meningitis represents 5% of extrapulmonary cases in the United States with the risk for tuberculosis increased six times for foreign-born persons. We report the case of a foreign-born cirrhotic patient with tuberculous meningitis whose diagnosis was likely delayed because of signs and symptoms of her underlying hepatic disease. PMID:12685697

Carmichael, Mark G; Thompson, Jennifer C; Buttolph, Thomas B; Hooke, Jeffrey A



Compartmentalization and antiviral effect of efavirenz metabolites in blood plasma, seminal plasma, and cerebrospinal fluid.  


Efavirenz (EFV) is one of the most commonly prescribed antiretrovirals for use in the treatment of human immunodeficiency virus (HIV) infection. EFV is extensively metabolized by cytochrome P450 to a number of oxygenated products; however, the pharmacologic activity and distribution of these metabolites in anatomic compartments have yet to be explored. The systemic distribution of EFV oxidative metabolites was examined in blood plasma, seminal plasma, and cerebrospinal fluid from subjects on an EFV-based regimen. The 8-hydroxy EFV metabolite was detected in blood plasma, seminal plasma, and cerebrospinal fluid, with median concentrations of 314.5 ng/ml, 358.5 ng/ml, and 3.37 ng/ml, respectively. In contrast, 7-hydroxy and 8,14-hydroxy EFV were only detected in blood plasma and seminal plasma with median concentrations of 8.84 ng/ml and 10.23 ng/ml, and 5.63 ng/ml and 5.43 ng/ml, respectively. Interestingly, protein-free concentrations of metabolites were only detectable in seminal plasma, where a novel dihdyroxylated metabolite of EFV was also detected. This accumulation of protein-free EFV metabolites was demonstrated to be the result of differential protein binding in seminal plasma compared with that of blood plasma. In addition, the oxidative metabolites of EFV did not present with any significant pharmacologic activity toward HIV-1 as measured using an HIV green fluorescent protein single-round infectivity assay. This study is the first to report the physiologic distribution of metabolites of an antiretroviral into biologic compartments that the virus is known to distribute and to examine their anti-HIV activity. These data suggest that the male genital tract may be a novel compartment that should be considered in the evaluation of drug metabolite exposure. PMID:23166317

Avery, Lindsay B; VanAusdall, Jennifer L; Hendrix, Craig W; Bumpus, Namandjé N



Aminoterminally truncated and oxidized amyloid-? peptides in the cerebrospinal fluid of Alzheimer's disease patients.  


Carboxyterminally elongated and aminoterminally truncated amyloid-? (A?) peptides and their oxidized derivates are major constituents of human amyloid plaques. The objective of the present study was to clarify the diagnostic impact of the A? peptides 1-38ox, 2-40, and 2-42 peptides on the neurochemical cerebrospinal fluid (CSF) diagnosis of Alzheimer's disease (AD). For this purpose, 22 patients with AD and 20 non-demented disease controls (NDC) were comparatively analyzed for their cerebrospinal fluid pattern of A?1-38ox, A?2-40, and A?2-42 along with A?1-37, A?1-38, A?1-39, A?1-40, A?1-40ox, and A?1-42 using a novel sequential aminoterminally and carboxyterminally specific immunoprecipitation protocol and subsequent analysis in the A?-SDS-PAGE/immunoblot. The A? peptides 1-38ox, 2-40, and 2-42 could not be consistently detected in the investigated CSF samples, which applied to samples from AD and NDC patients alike. Otherwise, our approach revealed a striking decrease of A?1-42 and A?2-42, but not of A?1-38ox and A?2-40 in AD. Both A?1-42 and A?2-42 reached reasonable accuracies for diagnosing AD alone as well as in relation to A?1-40, A?1-38, or the sum of all measured A? peptides. A?1-38ox was negatively correlated to the Mini-Mental Status Examination score of AD patients, indicating that this peptide to linked to disease severity. We conclude that an exact analysis of CSF A? peptides regarding their carboxy- and aminoterminus as well as posttranslational modification may be a promising approach for diagnosing and tracking AD. PMID:22460324

Bibl, Mirko; Gallus, Marion; Welge, Volker; Esselmann, Hermann; Wiltfang, Jens



Serum and Cerebrospinal Fluid Levels of Transthyretin in Lewy Body Disorders with and without Dementia  

PubMed Central

Parkinson’s disease (PD) without (non-demented, PDND) and with dementia (PDD), and dementia with Lewy bodies (DLB) are subsumed under the umbrella term Lewy body disorders (LBD). The main component of the underlying pathologic substrate, i.e. Lewy bodies and Lewy neurites, is misfolded alpha-synuclein (Asyn), and - in particular in demented LBD patients - co-occurring misfolded amyloid-beta (Abeta). Lowered blood and cerebrospinal fluid (CSF) levels of transthyretin (TTR) - a clearance protein mainly produced in the liver and, autonomously, in the choroid plexus - are associated with Abeta accumulation in Alzheimer’s disease. In addition, a recent study suggests that TTR is involved in Asyn clearance. We measured TTR protein levels in serum and cerebrospinal fluid of 131 LBD patients (77 PDND, 26 PDD, and 28 DLB) and 72 controls, and compared TTR levels with demographic and clinical data as well as neurodegenerative markers in the CSF. Five single nucleotide polymorphisms of the TTR gene which are considered to influence the ability of the protein to carry its ligands were also analyzed. CSF TTR levels were significantly higher in LBD patients compared to controls. Post-hoc analysis demonstrated that this effect was driven by PDND patients. In addition, CSF TTR levels correlated negatively with CSF Abeta1–42, total tau and phospho-tau levels. Serum TTR levels did not significantly differ among the studied groups. There were no relevant associations between TTR levels and genetic, demographic and clinical data, respectively. These results suggest an involvement of the clearance protein TTR in LBD pathophysiology, and should motivate to elucidate TTR-related mechanisms in LBD in more detail.

Gauger, Tina; Odoj, Bartholomaus; Schmid, Benjamin; Schulte, Claudia; Deuschle, Christian; Heck, Susanna; Apel, Anja; Melms, Arthur; Gasser, Thomas; Berg, Daniela



On the significance of monoamines and their metabolites in the cerebrospinal fluid of the sheep.  

PubMed Central

Assays capable of concurrently measuring small quantities of noradrenaline, dopamine, serotonin, and several of their metabolites in cerebrospinal fluid (c.s.f.) were developed by the use of high performance liquid chromatography with electrochemical detection. For comparison, cortical subarachnoid, ventricular, cisternal and lumbar c.s.f. were obtained by puncture under barbiturate anaesthesia in sheep. Basal concentrations related to the adrenergic system, including methoxyhydroxyphenylglycol (MHPG), were similar in ventricular, cisternal and lumbar c.s.f., and those of the serotoninergic metabolites, 5-hydroxyindole-3-acetylacetic acid (5-HIAA), were similar in ventricular and cisternal c.s.f. High concentrations of the dopamine metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found only in ventricular c.s.f. Monoamine metabolites in ventricular c.s.f. under basal conditions and after various experimental manipulations were then determined over periods of 3 months in two different breeds of sheep fitted chronically with cannulae in lateral ventricles. A dose-related accumulation of all the acidic monoamine metabolites was recorded during treatment with probenecid. The increase in 5-HIAA was linear after administration of increased doses of tryptophan and 5-hydroxytryptophan. The concentrations of dopamine, DOPAC and HVA in the ventricular c.s.f. reflected the response of the dopaminergic system to agents capable of crossing the blood-brain barrier. It is concluded that cerebral metabolism in conscious sheep could be indirectly approached by recording the concentration of end-products of dopamine metabolism in ventricular cerebrospinal fluid, obtained under conditions of minimal stress.

Ruckebusch, M; Sutra, J F



Attenuated antiaggregation effects of magnetite nanoparticles in cerebrospinal fluid of people with Alzheimer's disease.  


It is well known that oligomeric/aggregated amyloid ? peptides are a key player in the pathogenesis of Alzheimer's disease and that different nanoparticles influence oligomerization/aggregation processes in experiments in vitro. Our previous results demonstrated antiaggregation effects of magnetite nanoparticles in the case of protein lysozyme, however, they have yet to be supported by biological samples containing peptides/proteins preaggregated in vivo. In the study, Thioflavin T based fluorescence was evaluated on cerebrospinal fluid samples from people with Alzheimer's disease/multiple sclerosis and corresponding age-related controls using magnetite nanoparticles incubated for 24 h. Our results are as follows: (i) fluorescence of samples without nanoparticles was significantly higher in both older groups (old controls and people with Alzheimer's disease) than in those of younger (young controls and people with multiple sclerosis), (ii) nanoparticles did not markedly influence a fluorescence intensity in young people but eliminated it in both old groups; nevertheless, the effects of nanoparticles were significantly lower in patients with Alzheimer's disease then in the age-matched controls, and finally (iii) significant positive correlation was observed between fluorescence of samples without nanoparticles and levels of phospho-tau. Our results support studies reporting enhanced aggregation of different peptides/proteins occurring during normal aging and demonstrate for the first time that peptides/proteins preaggregated in vivo during Alzheimer's disease are more resistant to the antiaggregation effects of magnetite nanoparticles than those of age-matched controls. A significant correlation with phospho-tau levels indicate that the in vitro test with magnetite nanoparticles and Thioflavin T dye on cerebrospinal fluid could be sensitive to changes mediated by early Alzheimer's disease stages. PMID:20721410

Gažová, Zuzana; Antošová, Andrea; Krištofiková, Zdena; Bartoš, Aleš; Rí?ný, Jan; Cechová, Linda; Klaschka, Jan; Rípová, Daniela



Pseudocholinesterase activity in cerebrospinal fluid as a biomarker of solid central nervous system tumors in children.  


Aim. To determine the activity of pseudocholinesterase (PChE) in cerebrospinal fluid (CSF) and serum in children with solid central nervous system (CNS) tumor and to assess whether PChE activity could be a valid biomarker for solid CNS tumors in children. Methods. The study and control group included 30 children each. Children in the study group had a solid CNS tumor, while those from the control group had never suffered from any tumor diseases. CSF and serum samples were collected from all participants and PChE activity was determined using the Ellman's spectrophotometric method. PChE activity in CSF was shown as a cerebrospinal fluid/serum ratio expressed in percentage, ie, PChE CSF/serum ratio. Receiver operating characteristic (ROC) curve was used to assess whether PChE activity can be used as a biomarker for identifying children with solid CNS tumors. Results. Children with solid CNS tumor had significantly higher PChE activity in CSF and serum, as well as PChE CSF/serum ratio (P=0.001). PChE CSF/serum ratio in the study group was 2.38% (interquartile range [IQR] 1.14-3.97) and 1.09% (IQR 0.95-1.45) in the control group. ROC curve analysis of PChE CSF/serum ratio resulted in an area under the curve (AUC) value of 0.76 (95% confidence interval [CI] 0.63-0.88) and a cut-off of 1.09. Twenty five of 29 patients with elevated PChE CSF/serum ratio had a tumor, corresponding to a sensitivity of 83% and a specificity of 53%. Conclusion. PChE CSF/serum ratio may be used as a test or biomarker with good sensitivity for solid CNS tumors in children. PMID:24170721

Mikecin, Lili; Krizmaric, Miljenko; Stepan Giljevic, Jasminka; Gjurasin, Miroslav; Kern, Josipa; Lenicek Krleza, Jasna; Popovic, Ljiljana



Rapid Determination of Methadone in Plasma, Cerebrospinal Fluid, and Urine by Gas Chromatography and Its Application to Routine Drug Monitoring  

Microsoft Academic Search

Determination of methadone (MET) in biological fluids can serve to adjust dosages in patients suffering from cancer pain or participating in methadone maintenance programs. We developed a gas chromatographic assay using nitrogen-phosphorus detection. The method involves a single-step extraction from alkalized plasma, cerebrospinal fluid, or urine into n-hexane\\/isoamylalcohol (99\\/1, v\\/v). Dextropropoxyphene was used as internal standard. Separation was achieved with

Norbert Schmidt; Reinhard Sittl; Kay Brune; Gerd Geisslinger



Effects of irregular cerebrospinal fluid production rate in human brain ventricular system  

NASA Astrophysics Data System (ADS)

Hydrocephalus is an abnormal accumulation of fluid in the ventricles and cavities in the brain. It occurs when the cerebrospinal fluid (CSF) flow or absorption is blocked or when excessive CSF is secreted. The excessive accumulation of CSF results in an abnormal widening of the ventricles. This widening creates potentially harmful pressure on the tissues of the brain. In this study, flow analysis of CSF was conducted on a three-dimensional model of the third ventricle and aqueduct of Sylvius, derived from MRI scans. CSF was modeled as Newtonian Fluid and its flow through the region of interest (ROI) was done using EFD. Lab software. Different steady flow rates through the Foramen of Monro, classified by normal and hydrocephalus cases, were modeled to investigate its effects. The results show that, for normal and hydrocephalus cases, the pressure drop of CSF flow across the third ventricle was observed to be linearly proportionally to the production rate increment. In conclusion, flow rates that cause pressure drop of 5 Pa was found to be the threshold for the initial sign of hydrocephalus.

Hadzri, Edi Azali; Shamsudin, Amir Hamzah; Osman, Kahar; Abdul Kadir, Mohammed Rafiq; Aziz, Azian Abd



Hypothesis on the pathophysiology of syringomyelia based on simulation of cerebrospinal fluid dynamics  

PubMed Central

Objectives: Despite many hypotheses, the pathophysiology of syringomyelia is still not well understood. In this report, the authors propose a hypothesis based on analysis of cerebrospinal fluid dynamics in the spine. Methods: An electric circuit model of the CSF dynamics of the spine was constructed based on a technique of computational fluid mechanics. With this model, the authors calculated how a pulsatile CSF wave coming from the cranial side is propagated along the spinal cord. Results: Reducing the temporary fluid storage capacity of the cisterna magna dramatically increased the pressure wave propagated along the central canal. The peak of this pressure wave resided in the mid-portion of the spinal cord. Conclusions: The following hypotheses are proposed. The cisterna magna functions as a shock absorber against the pulsatile CSF waves coming from the cranial side. The loss of shock absorbing capacity of the cisterna magna and subsequent increase of central canal wall pressure leads to syrinx formation in patients with Chiari I malformation.

Chang, H; Nakagawa, H



Cisterna magna microdialysis of sup 22 Na to evaluate ion transport and cerebrospinal fluid dynamics  

SciTech Connect

Microdialysis is used in vivo for measuring compounds in brain interstitial fluid. The authors describe another application of this technique to the central nervous system, namely microprobe dialysis in the cisterna magna to study the dynamics of ion transport and cerebrospinal fluid (CSF) formation in the rat. The choroid plexus is the major source of CSF, which is produced by active transport of Na from blood into the cerebral ventricles. Formation of CSF is directly proportional to the blood-to-CSF transport of Na. By injecting {sup 22}Na into the systemic circulation and quantifying its movement into CSF by microdialysis, one can reliably estimate alterations in the rate of CSF formation. The sensitivity of this system was determined by administering acetazolamide, a standard inhibitor of CSF production. Because acetazolamide is known to decrease CSF formation by 40% to 50%, the cisternal microdialysis system in animals treated with this drug should detect a corresponding decrease in the amount of {sup 22}Na dialyzed. This hypothesis is supported by the {sup 22}Na uptake curves for control versus treated animals: that is, by the acetazolamide-induced average diminution of about 45% in both the rate and extent of tracer accession to dialysate. Bumetanide, a loop diuretic, reduced by 30% the {sup 22}Na entry into dialysate. Microprobe dialysis of fluid in the cisterna magna is thus a minimally invasive and economical method for evaluating effects of drugs and hormones on the choroid plexus-CSF system.

Knuckey, N.W.; Fowler, A.G.; Johanson, C.E.; Nashold, J.R.; Epstein, M.H. (Brown Univ./Rhode Island Hospital, Providence (USA))



Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer's disease.  


Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer's disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses. PMID:23868911

Fonteh, Alfred N; Chiang, Jiarong; Cipolla, Matthew; Hale, Jack; Diallo, Fatimatou; Chirino, Alejandra; Arakaki, Xianghong; Harrington, Michael G



Kinetics of ofloxacin and its metabolites in cerebrospinal fluid after a single intravenous infusion of 400 milligrams of ofloxacin.  

PubMed Central

Ofloxacin has been reported to diffuse readily into the cerebrospinal fluid (CSF) in subjects with both inflamed and uninflamed meninges. However, with moderately susceptible bacteria, ofloxacin concentrations in CSF may be subtherapeutic after administration of an intravenous (i.v.) dose of 200 mg. For this reason, the kinetics of a higher dose of ofloxacin in CSF was studied with humans. Six patients with occlusive hydrocephalus caused by cerebrovascular diseases who had undergone external ventriculostomy received 400 mg of ofloxacin i.v. over 30 min. Serum and CSF samples were drawn repeatedly. Serum from 12 healthy volunteers was sampled repeatedly after they had received 400 mg of ofloxacin i.v. over 60 min. Ofloxacin, ofloxacin-N-oxide, and N-desmethyl-ofloxacin concentrations were determined by high-pressure liquid chromatography with fluorescence detection. The maximum ofloxacin concentrations in the serum of the patients ranged from 7.36 to 11.6 mg/liter (mean, 9.55 mg/liter), the apparent volume of distribution/body weight was 0.96 to 1.19 liters/kg (mean, 1.11 liters/kg), and the total body clearance was 115 to 280 ml/min (mean, 192 ml/min). In healthy volunteers, the volume of distribution/body weight and the total body clearance were higher and amounted to 1.27 +/- 0.18 liters/kg and 217 +/- 43 ml/min (means +/- standard deviations), respectively. These differences were attributed to the older ages of the patients than the volunteers. In the CSF of patients, maximum concentrations of 1.00 to 2.85 mg/liter (mean, 2.04 mg/liter) were observed 0.5 to 4 h following the completion of the ofloxacin infusion. Ofloxacin elimination from CSF was slightly slower than that from serum (half-lives, 4.33 to 10.02 versus 4.27 to 9.14 h). The overall penetration of ofloxacin into CSF, as expressed by the ratios of the areas under the concentration-curves, amounted to 0.59 to 0.81 (mean, 0.65). The more hydrophilic metabolites ofloxacin-N-oxide and N-desmethyl-ofloxacin passed less readily than ofloxacin into the CSF. In conclusion, the concentrations in CSF attained after a single i.v. infusion of 400 mg of ofloxacin in the absence of meningeal inflammation appear to be high enough to inhibit the growth of most staphylococci and members of the family Enterobacteriaceae, which are often involved in CSF shunt infection. Yet, in view of pharmacodynamic studies suggesting a peak concentration in CSF of at least 10-fold the MIC, the use of ofloxacin for central nervous systems infections is optimal only with highly susceptible pathogens (MIC, less than or equal to 0.12 mg/liter).

Nau, R; Kinzig, M; Dreyhaupt, T; Kolenda, H; Sorgel, F; Prange, H W



Meningitis due to Rhodotorula glutinis in an HIV infected patient.  


Rhodotorula spp, though considered a common saprophyte, recently has been reported as causative agent of opportunistic mycoses. We present a case of meningitis in an immunocompromised human immunodeficiency virus infected patient who presented with longstanding fever. He was diagnosed as a case of chronic meningitis. Diagnosis was confirmed by cell cytology, India ink preparation, Gram staining and culture of cerebrospinal fluid (CSF) sample. CSF culture grew Rhodotorula glutinis. Therapy with amphotericin B was successful in eliminating the yeast from CSF and the patient was discharged after recovery. PMID:18974495

Shinde, R S; Mantur, B G; Patil, G; Parande, M V; Parande, A M


Enrichment of cerebrospinal fluid samples on cell culture for enhancement of sensitivity of mumps and enterovirus detection by multiplex RT-PCR.  


It has been demonstrated that the detection of enteroviruses and mumps virus nucleic acid in cerebrospinal fluid (CSF) specimens improves the management of the patients with aseptic meningitis. To determine the effect of overnight enrichment of mumps and enteroviruses in CSF samples on cell culture for increasing the sensitivity of viral detection, we developed a multiplex reverse transcriptase-polymerase chain reaction (RT-PCR). CSFs were collected from 100 patients younger than 7 years. The samples were tested for the presence of enteroviruses and mumps virus by multiplex RT-PCR method. Negative samples in Multiplex RT-PCR were enriched for viral template RNAs by overnight culture of CSF samples on cells and followed by the optimized Multiplex RT-PCR. Overall, 35% of the CSF samples were positive for enteroviruses, whereas only 1% of CSF samples were positive for both viruses. After enriching in cell culture, 34% of the negative samples showed a positive polymerase chain reaction band for enteroviruses, and a 3% increase was observed for both viruses. The results showed that enrichment of viral template RNAs in cell culture can increase the sensitivity of the multiplex RT-PCR assay and provide a rapid and sensitive method for detection of viral infections. PMID:18083320

Kermanian, Masoumeh; Soleimanjahi, Hoorieh; Arefian, Ehsan; Bamdad, Taravat



Salmonella meningitis in an immunocompetent adult.  


Non-enteric salmonella infections in immunocompetent adults are exceedingly rare in the United States, and meningitis is one of the least common extra-intestinal sites. In addition, it is very unusual for a patient with bacterial meningitis to present with classic meningitis signs and symptoms of > 72 h duration. The objective of this work is to describe a rare case of salmonella meningitis in an immunocompetent adult and, in the context of previously published case reports, describe the frequently atypical clinical course of salmonella meningitis along with the potential pitfalls encountered during its evaluation and treatment. An otherwise healthy 45-year-old man presented to our Emergency Department with frontal headache, fever, and stiff neck of 7 days duration. He was alert and oriented in triage, where he was noted to be afebrile, mildly tachycardic, with a normal blood pressure and respiratory rate; shortly after triage he developed a high fever, severe tachycardia, hypotension, and a change in mental status. He was resuscitated according to our severe sepsis protocol and treated empirically for bacterial meningitis. Blood and cerebrospinal fluid cultures grew group D Salmonella berta. An evaluation for underlying immunodeficiency was unrevealing. The patient was discharged home on hospital day 7 in good condition. Salmonella meningitis can present with an indolent course and can mimic, in many misleading ways, the less serious diagnosis of aseptic meningitis. This case highlights the need for an unbiased clinical assessment, aggressive management of critical illness, and point-for-point correspondence between clinical data and assigned diagnosis. PMID:18534805

Carr, Brendan G; Weisbein, Jessica L; Gaieski, David F



Cryptococcus meningoencephalitis in AIDS: parenchymal and meningeal forms  

Microsoft Academic Search

CT and MRI in one case of Cryptococcus neoformans infection showed contrast-enhancing parenchymal lesions resembling granulomata or abscesses. After an initial phase without\\u000a contrast enhancement, the full extent of the lesions was visible within 2 weeks of presentation. The enhancing masses were\\u000a assumed to represent intracerebral cryptococcomas. Despite evidence of massive meningeal infection on cerebrospinal fluid\\u000a (CSF) examination, no radiological

J. Berkefeld; W. Enzensberger; H. Lanfermann



Three Cases of Neoplastic Meningitis Initially Diagnosed with Infectious Meningitis in Emergency Department  

PubMed Central

Neoplastic meningitis (NM) is diagnosed by the presence of malignant cells in the cerebrospinal fluid (CSF). We report 3 patients with NM, who were misdiagnosed with infectious meningitis in emergency department (ED). Case 1. A 68-year-old man visited our ED with a 3-month history of headache. With MRI and CSF study, he was diagnosed with tuberculous meningitis. After 20 days, repeated CSF cytology showed malignant cells. His diagnosis was lung cancer with NM. Case 2. A 57-year-old man visited regional hospital ED with a 3-week history of headache and diplopia. Brain MRI was not contributory. With CSF examination, his diagnosis was aseptic meningitis. With worsening headache, he was referred to our ED. Repeated CSF showed malignant cells. His diagnosis was stomach cancer with NM. Case 3. A 75-year-old man visited a regional hospital with headache lasting for 4 months. His diagnosis was sinusitis. Persistent symptom brought him back, and he developed recurrent generalized seizures. Brain MRI showed diffuse leptomeningeal enhancement suggesting meningitis, and he was transferred to our ED. CSF exam showed malignant cells. His diagnosis was NM with unknown primary focus. When evaluating the patients with headache in ED, NM should be kept in mind as a differential diagnosis of meningitis.

Lim, Kyung Soo



Case-fatality ratio of bacterial meningitis in the African meningitis belt: we can do better.  


In the African meningitis belt, reported case-fatality ratio (CFR) for meningitis are usually calculated on the basis of presumed cases. We reviewed 3509 presumed cases of bacterial meningitis reported in Niger for which a cerebrospinal fluid (CSF) sample had been tested later at the reference laboratory. The main aetiologies were Neisseria meningitidis (1496 cases), Streptococcus pneumoniae (303 cases) and Haemophilus influenzae (105 cases). The CFR of meningococcal meningitis was lower for serogroup A (5.5%) than for serogroups X (12%) and W135 (12.7%). With a CFR of 49.8%, pneumococcal meningitis, albeit representing only 20.7% of confirmed cases, accounted for 50% of the deaths. The disease burden of pneumococcal meningitis must be better taken into consideration in the future. As most treatments are presumptive, there is a urgent need for an easy-to-administer, cheap first-line treatment effective on N. meningitidis as well as on S. pneumoniae and H. influenzae that would replace the single-dose oily chloramphenicol treatment which is the most frequent treatment administered today, independent of microbial aetiology and season. The development of diagnostic tools really suitable for remote health facilities also is an urgent challenge. PMID:17521784

Boisier, Pascal; Maïnassara, Halima Boubacar; Sidikou, Fati; Djibo, Saacou; Kairo, Kiari Kaka; Chanteau, Suzanne



Cerebrospinal fluid ionic regulation, cerebral blood flow, and glucose use during chronic metabolic alkalosis  

SciTech Connect

Chronic metabolic alkalosis was induced in rats by combining a low K+ diet with a 0.2 M NaHCO3 solution as drinking fluid for either 15 or 27 days. Local cerebral blood flow and local cerebral glucose utilization were measured in 31 different structures of the brain in conscious animals by means of the iodo-(14C)antipyrine and 2-(14C)deoxy-D-glucose method. The treatment induced moderate (15 days, base excess (BE) 16 mM) to severe (27 days, BE 25 mM) hypochloremic metabolic alkalosis and K+ depletion. During moderate metabolic alkalosis no change in cerebral glucose utilization and blood flow was detectable in most brain structures when compared with controls. Cerebrospinal fluid (CSF) K+ and H+ concentrations were significantly decreased. During severe hypochloremic alkalosis, cerebral blood flow was decreased by 19% and cerebral glucose utilization by 24% when compared with the control values. The decrease in cerebral blood flow during severe metabolic alkalosis is attributed mainly to the decreased cerebral metabolism and to a lesser extent to a further decrease of the CSF H+ concentration. CSF K+ concentration was not further decreased. The results show an unaltered cerebral blood flow and glucose utilization together with a decrease in CSF H+ and K+ concentrations at moderate metabolic alkalosis and a decrease in cerebral blood flow and glucose utilization together with a further decreased CSF H+ concentration at severe metabolic alkalosis.

Schroeck, H.K.; Kuschinsky, W. (Univ. of Bonn (Germany, F.R.))



Quantification of the cerebrospinal fluid from a new whole body MRI sequence  

NASA Astrophysics Data System (ADS)

Our work aims to develop a biomechanical model of hydrocephalus both intended to perform clinical research and to assist the neurosurgeon in diagnosis decisions. Recently, we have defined a new MR imaging sequence based on SPACE (Sampling Perfection with Application optimized Contrast using different flip-angle Evolution). On these images, the cerebrospinal fluid (CSF) appears as a homogeneous hypersignal. Therefore such images are suitable for segmentation and for volume assessment of the CSF. In this paper we present a fully automatic 3D segmentation of such SPACE MRI sequences. We choose a topological approach considering that CSF can be modeled as a simply connected object (i.e. a filled sphere). First an initial object which must be strictly included in the CSF and homotopic to a filled sphere, is determined by using a moment-preserving thresholding. Then a priority function based on an Euclidean distance map is computed in order to control the thickening process that adds "simple points" to the initial thresholded object. A point is called simple if its addition or its suppression does not result in change of topology neither for the object, nor for the background. The method is validated by measuring fluid volume of brain phantoms and by comparing our volume assessments on clinical data to those derived from a segmentation controlled by expert physicians. Then we show that a distinction between pathological cases and healthy adult people can be achieved by a linear discriminant analysis on volumes of the ventricular and intracranial subarachnoid spaces.

Lebret, Alain; Petit, Eric; Durning, Bruno; Hodel, Jérôme; Rahmouni, Alain; Decq, Philippe



Production and circulation of cerebrospinal fluid with respect to the subarachnoid space of the optic nerve.  


The function of cerebrospinal fluid (CSF) is to protect the brain and optic nerve from mechanical damage, provide nutrition for axons/neurons, and remove of toxic metabilites. CSF is produced mainly by the choroid plexus epithelium and ependymal cells of the ventricles and flows into interconnecting chambers; namely, the cisterns and the subarachnoid spaces. Based on studies of CSF circulation and direction of flow using radioisotopes and other tracers injected into the CSF, it is thought that there is a bulk circulation of fluid from the sites of production in the third, fourth, and lateral ventricles to the arachnoid villi and probably to the lymphatic capillaries in the cranial dura mater. The mechanism by which CSF is propelled is incompletely understood, but probably is influenced by the release of newly produced CSF, ventricular pulsations, and the pulse pressure of the vascular choroid plexus. This mechanism would account for the steady CSF pressure. In addition to the steady CSF pressure, overlapping pressure spikes occur during trunk inclination, coughing and other valsalva. PMID:23733131

Killer, Hanspeter E


Neonatal bacterial meningitis.  


Neonatal bacterial meningitis (NM) continues to be a serious disease with an unchanging rate of adverse outcome of 20-60%, despite a worldwide decline in mortality. The 3 major pathogens in developed countries are: Group B streptococcus, gram negative rods and Lysteria monocytogenes. Signs and symptoms of NM may be subtle, unspecific, vague, atypical or absent. In order to exclude NM, all infants with proven or suspected sepsis should undergo lumbar puncture. Positive culture of cerebrospinal fluid may be the only way to diagnose NM and to identify the pathogen, as CSF parameters Smay be normal at early stages and NM may occur frequently (up to 30% of cases) in the absence of bacteraemia. When NM is suspected, treatment must be aggressive, as the goal is to achieve bactericidal concentration of antibiotics and to sterilize CSF as soon as possible. Antibiotics should be administered intravenously, at the highest clinically validated doses. Empiric antibiotic treatment should include agents active against all main pathogens; currently the recommended empiric treatment of NM is ampicillin, plus an aminoglycoside and a third-generation cephalosporn. Therapy should be reassessed after cultures and antibiotic susceptibility is available. Prevention of neonatal sepsis, early recognition of infants at risk, prompt treatment and future adjunctive therapies will improve prognosis. Finally, we present the first preliminary Italian data on GBS meningitis. Data are obtained from an area-based study conducted In Emilia-Romagna during 2003 to 2009. PMID:21089719

Berardi, A; Lugli, L; Rossi, C; China, M C; Vellani, G; Contiero, R; Calanca, F; Camerlo, F; Casula, F; Di Carlo, C; Rossi, M R; Chiarabini, R; Ferrari, M; Minniti, S; Venturelli, C; Silvestrini, D; Dodi, I; Zucchini, A; Ferrari, F



Aseptic meningitis after transsphenoidal management of Rathke's cleft cyst: case report and review of the literature.  


Aseptic meningitis after transsphenoidal surgery (TSS) for treatment of Rathke's cleft cyst (RCC) is a rare complication caused by the leakage of the cyst contents within the subarachnoid space. We present a case of aseptic meningitis occurring after TSS for a RCC. During surgery, the cyst wall was subtotally removed, and intraoperative cerebrospinal fluid (CSF) leakage was observed. The patient developed meningeal signs and symptoms on the first postoperative day. CSF examinations were highly suggestive of aseptic meningitis. Histological examination confirmed a granulomatous inflammatory reaction of the RCC wall. Preexisting inflammation, subtotal cyst wall resection, intraoperative erosion of the diaphragma sellae and placement of a lumbar drain may be risk factors for the development of aseptic meningitis. PMID:21234780

Koutourousiou, Maria; Seretis, Andreas



Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem  

PubMed Central

Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment.

Orts-Del'Immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jerome



Properties of subependymal cerebrospinal fluid contacting neurones in the dorsal vagal complex of the mouse brainstem.  


Cerebrospinal fluid (CSF) contacting neurones have been observed in various brain regions such as the hypothalamus, the dorsal nucleus of the raphe and around the central canal (cc) of the spinal cord but their functional role remains unclear. At the level of the spinal cord, subependymal cerebrospinal fluid contacting neurones (S-CSF-cNs) present a peculiar morphology with a soma close to the ependymal layer, a process projecting towards the cc and ending with a bud and a cilium. These neurones were recently shown to express polycystin kidney disease 2-like 1 (PKD2L1 or TRPP3) channels that are members of the polycystin subtype of the transient receptor potential (TRP) channel superfamily and that have been proposed as either chemo- or mechanoreceptors in several tissues. Using immunohistological techniques and whole-cell electrophysiological recordings in brain slices obtained from PKD2L1:EGFP transgenic adult mice, we looked for and determined the functional properties of S-CSF-cNs in the dorsal vagal complex (DVC), a hindbrain structure controlling autonomic functions such as blood pressure, energy balance and food intake. Here, we demonstrate that S-CSF-cNs received GABAergic and/or glycinergic synaptic entries and were also characterised by the presence of non-selective cationic channels of large conductance that could be detected even under whole-cell configuration. The channel activity was not affected by Psalmopoeus cambridgei toxin 1, a blocker of acid sensing ion channels (ASICs), but was blocked by amiloride and by a strong extracellular acidification. In contrast, extracellular alkalinisation and hypo-osmotic shocks increased channel activity. Based on these properties, we suggest that the single-channel activity recorded in medullar S-CSF-cNs is carried by PKD2L1 channels. Our study therefore reinforces the idea that PKD2L1 is a marker of S-CSF-cNs and points toward a role for S-CSF-cNs in the detection of circulating signals and of modifications in the extracellular environment. PMID:22570378

Orts-Del'immagine, Adeline; Wanaverbecq, Nicolas; Tardivel, Catherine; Tillement, Vanessa; Dallaporta, Michel; Trouslard, Jérôme



Adenine nucleotide hydrolysis in patients with aseptic and bacterial meningitis.  


The meningitis is a disease with high mortality rates capable to cause neurologic sequelae. The adenosine (the final product of ATP hydrolysis by ectonucleotidases), have a recognized neuroprotective actions in the central nervous system (CNS) in pathological conditions. The aim of the present study was evaluate the adenine nucleotides hydrolysis for to verify one possible role of ATP, ADP and AMP hydrolysis in inflammatory process such as meningitis. The hydrolysis was verified in cerebrospinal fluid (CSF) from human patients with aseptic and bacterial meningitis. Our results showed that the ATP hydrolysis was reduced 12.28% (P < 0.05) in bacterial meningitis and 22% (P < 0.05) in aseptic meningitis. ADP and AMP hydrolysis increased 79.13% (P < 0.05) and 26.37% (P < 0.05) in bacterial meningitis, respectively, and 57.39% (P < 0.05) and 42.64% (P < 0.05) in aseptic meningitis, respectively. This may be an important protective mechanism in order to increase adenosine production. PMID:18712598

Dorneles, Aracélli Gnatta; Menezes, Charlene; Sperotto, Rita Leal; Duarte, Marta Medeiros Frescura; Morsch, Vera Maria; Schetinger, Maria Rosa Chitolina; Loro, Vânia Lúcia



Alteration of cystatin C levels in cerebrospinal fluid of patients with Guillain-Barré Syndrome by a proteomical approach  

Microsoft Academic Search

Objective To better understand the pathophysiological mechanisms underlying Guillain-Barré Syndrome (GBS) and to ascertain the protein\\u000a that presents with the most observable changes in the cerebrospinal fluid (CSF) of patients GBS. Methods we analyzed individually the proteomes of CSF of patients with GBS (the experiment group) and control subjects suffering\\u000a from other neurological disorders (the control group) with two-dimensional gel

Yinrong Yang; Shilian Liu; Zhaoyu Qin; Yazhou Cui; Yanjiang Qin; Shumei Bai



High-performance liquid chromatographic method for determination of 2-difluoromethyl- dl-ornithine in plasma and cerebrospinal fluid  

Microsoft Academic Search

A simple, sensitive, selective and reproducible method based on anion-exchange liquid chromatography with post-column derivatisation was developed for the determination of eflornithine (2-difluoromethyl-dl-ornithine; DFMO) in human plasma and cerebrospinal fluid. The 1-alkylthio-2-alkyl-isoindoles fluorescent derivative of the drug was separated from the internal standard (MDL 77246A) on an anion-exchange column (PRP-X300, 250×2.1 mm, 7-?m particle size: Hamilton, USA), with retention times

W Hanpitakpong; B Kamanikom; V Banmairuroi; K Na-Bangchang



An amino acid mixture deficient in phenylalanine and tyrosine reduces cerebrospinal fluid catecholamine metabolites and alcohol consumption in vervet monkeys  

Microsoft Academic Search

An amino acid mixture devoid of tryptophan, given orally, was previously shown to reduce cerebrospinal fluid levels of tryptophan\\u000a and 5-hydroxyindoleacetic acid in vervet monkeys, as compared to a control mixture containing all essential amino acids. In\\u000a the present study, we tested the possibility that a similar amino acid mixture containing tryptophan, but devoid of phenylalanine\\u000a and tyrosine (the amino

R. M. Palmour; Frank R. Ervin; Glen B. Baker; Simon N. Young



Cerebrospinal fluid otorrhoea from an abnormal communication between the internal auditory meatus and the medial wall of the tympanic cavity.  


Patients who have had middle-ear or mastoid surgery are at an increased risk of developing cerebrospinal fluid (CSF) otorrhoea. The CSF leak is usually from defects in the tegmen or posterior cranial fossa. We present a patient with CSF otorrhoea following a modified radical mastoidectomy seven years ago. There was an unusual communication between the internal auditory meatus (IAM) and the middle ear. Radiologic imaging like the MRI is useful in identifying the site of leak. PMID:20527282

Philip, R; Prepageran, N; Raman, R; Waran, V



Cerebrospinal fluid levels of tau phosphorylated at threonine 181 in patients with Alzheimer’s disease and vascular dementia  

Microsoft Academic Search

In 31 patients with probable Alzheimer’s disease (AD), 19 with probable vascular dementia (VaD) and 20 with Possible AD and\\u000a Possible VaD, cerebrospinal fluid (CSF) tau levels hyperphosphorylated at threonine 181 (Ptau) were measured by ELISA. Thirty-six\\u000a age-matched subjects were used as controls. The severity of the cognitive decline was assessed at the time of CSF analysis\\u000a and after a

Sabrina Ravaglia; Paola Bini; Elena Sinforiani; Diego Franciotta; Elisabetta Zardini; Pietro Tosca; Arrigo Moglia; Alfredo Costa



Tumor necrosis factor-?, interleukin-1?, and interleukin-6 in the cerebrospinal fluid of patients with cervical myelopathy and lumbar radiculopathy  

Microsoft Academic Search

There have been few reports describing cytokines in the cerebrospinal fluid (CSF) of patients with spinal degenerative disorders.\\u000a This study investigated whether interleukin-1? (IL-1?), interleukin-6 (IL-6), and tumor necrosis factor-? (TNF-?) could be\\u000a detected in CSF of patients with cervical myelopathy or lumbar radiculopathy and whether the concentrations of those cytokines\\u000a correlated with the severity of disease conditions. CSF samples

Hideki Nagashima; Yasuo Morio; Koji Yamane; Yoshiro Nanjo; Ryota Teshima



Concentrations of Metals, ?-Amyloid and Tau-Markers in Cerebrospinal Fluid in Patients with Alzheimer’s Disease  

Microsoft Academic Search

Background\\/Aims: In this study, metal concentrations were related to the levels of well-known Alzheimer markers in cerebrospinal fluid (CSF), such as amyloid-beta (A?), total tau (T-tau) and phosphorylated-tau (P-tau). Methods: Concentrations of 19 metals (Mg, Ca, V, Mn, Fe, Co, Ni, Cu, Zn, Se, Rb, Sr, Mo, Cd, Sn, Sb, Cs, Hg and Pb by inductively coupled plasma-mass spectrometry) and

Lars Gerhardsson; Kaj Blennow; Thomas Lundh; Elisabet Londos; Lennart Minthon



Cerebrospinal Fluid Concentrations of Somatostatin and Biogenic Amines in Grown Primates Reared by Mothers Exposed to Manipulated Foraging Conditions  

Microsoft Academic Search

Background: In an earlier study, infant primates were nursed by mothers randomly assigned to variable forag- ing demand (VFD) or nonvariable foraging conditions (non-VFD). A group of grown VFD-reared subjects demonstrated elevations of cisternal cerebrospinal fluid (CSF) corticotropin-releasing factor concentra- tions and decreased CSF cortisol levels vs non-VFD counterparts. To further characterize neurobiological sequelae of disturbed early rearing, CSF concentrations

Jeremy D. Coplan; Ronald C. Trost; Michael J. Owens; Thomas B. Cooper; Jack M. Gorman; Charles B. Nemeroff; Leonard A. Rosenblum



Relationship between presence of vasoconstrictor activity in cerebrospinal fluid and time after subarachnoid haemorrhage from rupture of cerebral arterial aneurysms.  

PubMed Central

The relationship between clinical condition and vasoconstrictor factors in cerebrospinal fluid was studied in 19 patients for up to six weeks after subarachnoid haemorrhage. Vasoconstrictor activity was assayed biologically. Sixteen of 19 patients improved as vasoconstrictor activity declined; this pattern was not significantly influenced by surgery. Serial angiography was performed on three patients and a qualitative relationship was shown between arterial dilatation, clinical improvement, and reduced pharmacological activity.

Hunt, T M; Du Boulay, G H; Blaso, W P; Forster, D M; Boullin, D J



Kinetics of Entry and Distribution of 5Fluorouracil in Cerebrospinal Fluid and Brain following Intravenous Injection in a Primate1  

Microsoft Academic Search

SUMMARY The distribution of systemically or locally administered 5-fluorouracil-2-14C (5-FU) in brain and cerebrospinal fluid (CSF) of the monkey (Macaca mulatta) has been investiga ted. Following controlled i.v. injection, there was rapid penetration of the 5-FU into brain and CSF, concomitant with a rapid loss of 5-FU from the systemic plasma compartment. CSF repeatedly sampled from various sites (lumbar, cisternal,

Robert S. Bourke; Charles R. West; Girish Chheda; Donald B. Tower